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Analysis of electroencephalogram (EEG) is a crucial diagnostic criterion for many sleep disorders, of which sleep staging is an important component. Manual stage classification is a labor-intensive process and usually suffered from many subjective factors. Recently, more and more computer-aided techniques have been applied to this task, among which deep convolutional neural network has been performing well as an effective automatic classification model. Despite some comprehensive models have been developed to improve classification results, the accuracy for clinical applications has not been reached due to the lack of sufficient labeled data and the limitation of extracting latent discriminative EEG features. Therefore, we propose a novel hybrid manifold-deep convolutional neural network with hyperbolic attention. To overcome the shortage of labeled data, we update the semi-supervised training scheme as an optimal solution. In order to extract the latent feature representation, we introduce the manifold learning module and the hyperbolic module to extract more discriminative information. Eight subjects from the public dataset are utilized to evaluate our pipeline, and the model achieved 89% accuracy, 70% precision, 80% sensitivity, 72% f1-score and kappa coefficient of 78%, respectively. The proposed model demonstrates powerful ability in extracting feature representation and achieves promising results by using semi-supervised training scheme. Therefore, our approach shows strong potential for future clinical development.

There is controversy regarding the long-term prognosis and short-term postoperative complications of different surgical strategies for proximal gastric cancer (PGC).We searched for articles published in Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science between January 1, 1990, and February 1, 2021. We screened out the literature comparing different surgical strategies. We then evaluated the long-term and short-term outcome of different surgical strategies using a network meta-analysis, which summarizes the hazard ratio, odds ratio, mean difference, and 95% confidence interval.There were no significant differences between different surgical strategies for 5-year overall survival (OS), anastomotic leakage, or weight loss after 1 year. Compared with total gastrectomy with Roux-en-Y reconstruction (TG-RY) and proximal gastrectomy with double tract reconstruction (PG-DTR), the proximal gastrectomy with esophagogastrostomy (PG-EG) strategy significantly increased the incidence of reflux esophagitis; and the operation time and blood loss of the PG-EG strategy were significantly less than those of the other surgical strategies. The anastomotic stenosis rates of the PG-EG and proximal gastrectomy with jejunum interstitial (PG-JI) strategies were significantly higher than those of TG-RY and PG-DTR; the hemoglobin level after 1 year for the PG-DTR strategy was significantly higher than that of the TG-RY strategy.Our comprehensive literature research found that different surgical strategies had no significant difference in the long-term survival of PGC, but the incidence of reflux esophagitis and anastomotic stenosis after PG-DTR and TG-RY was significantly reduced.

Lung cancer is a fatal disease with high morbidity and mortality. As a major type of non-small cell lung cancer (NSCLC), lung adenocarcinoma (LUAD) has come into the focus of the biological and clinical research. Nevertheless, potential functions of N6-methyladenosine (m6A) methylation-related long non-coding RNAs (lncRNAs) in the tumor immune microenvironment (TIME) remain unclear. Here, we analyzed RNA-seq data of 522 samples from the TCGA-LUAD project. Based on integrative analyses of lncRNA, immune, and clinical profiles, we developed a computational method to determine the characteristics of lncRNAs as an indicators of immune cell infiltration in LUAD patients. Subsequently, we investigated the influence of m6A-related lncRNAs on prognosis and immunotherapy in patients with LUAD. We identified 24 m6A-related lncRNAs that were related to LUAD prognosis and clustered in two molecular subtypes (clusters 1 and 2). Our results suggest that cluster 1 was significantly related to downregulation of PD-L1, enhancement of immune cell infiltration, and good prognosis. Furthermore, p53 and mTOR pathways were enriched in cluster 1, whereas in the cluster 2, PPAR was uncommonly enriched. Patients with LUAD who had lower risk scores exhibited higher immunoscores and lower expression levels of programmed cell death-ligand 1, compared with patients who had higher risk scores. Finally, m6A-related lncRNAs were implicated in the TIME; our findings indicate that these lncRNAs are critical within the TIME in LUAD. These signatures are promising as potential targets for improved LUAD immunotherapy.

The regeneration of myelin sheaths is the ultimate goal of the treatment of demyelination disease, including multiple sclerosis (MS). However, current drugs for MS mainly target the immune system and can only slow down the disease development and do not promote the differentiation of oligodendrocyte precursor cells (OPCs) abundant in the myelin injury region into mature oligodendrocytes to form a new myelin sheath. Brain-derived neurotrophic factor (BDNF) plays an important role in the regulation of OPC proliferation and differentiation into mature oligodendrocytes. Exosomes, a kind of nanoscale membrane vesicle secreted by cells, can be used as potential therapeutic drug delivery vectors for central nervous system diseases. Here, brain-targeted modification and BDNF intracellular-loaded exosomes were produced through engineering HEK293T cells, which can promote the differentiation of OPCs into mature oligodendrocytes

Objective In order to create a comprehensive scoring system based on maternal characteristics and ultrasonographic features for predicting placenta accreta spectrum (PAS). Materials and methods This was a retrospective review of pregnant women who underwent routine ultrasound examination in the third trimester of pregnancy from January 2014 to November 2018 were used as a training set to establish the scoring system for PAS prediction while those who underwent examination from January 2019 to December 2019 served as a validation set.. Maternal characteristics including maternal age, parity, previous vaginal deliveries, previous curettage, previous cesarean section (CS), history of hypertension and diabetes mellitus, prenatal body mass index (BMI) were recorded. Ultrasonographic features including abnormal placental lacunae, subplacental hypervascularity, myometrial thinning, placental bulge, bladder wall interruption, location of placenta, placenta previa (yes or not) were recorded. Multivariate analysis was applied to analyze independent risk factors and assess the predictive power of selected parameters predicting PAS. Receiver operating characteristics (ROC) curve was used to evaluate the diagnosis power. Results Parity, previous curettage and CS were independent risk factors. The best comprehensive scoring system was established as follow: the number of abnormal lacunae ≥3, 2 points; lacuna maximum dimension ≥2 cm, 5 points; subplacental hypervascularity (rich), 1 point; subplacental hypervascularity (extremely rich and disordered), 3 points; bladder wall interruption, 9 points; placental bulge, 9 points; placenta previa, 8 points; anterior placenta, 1 point; previous CS ≥ 1, 1 point; parity ≥ 4, 3 point; previous abortions ≥ 2, 1 point. The area under the ROC curve of the scoring system diagnosing PAS was 0.925. Sensitivity and specificity were 83.3% and 85.7%, respectively. Cross-validation for our model showed that sensitivity, specificity, positive predictive value and negative predictive value of the model in diagnosis of PAS were 82.6%, 81.8%, 82.6% and 81.8%, respectively. Diagnosis of 37 cases were consistent with the “gold standard”, and the coincidence rate was 82.2% (37/45). Conclusion The comprehensive scoring system established in this study can effectively diagnose PAS.

BackgroundFamily physicians play a key role in responding to the growing demand for primary healthcare due to aging. The work attitude of family physician team members (FPTMs) impacts their work efficiency and quality. Knowing how satisfied they are with their jobs can help identify potential directions and entry points for incentives. The purpose of this study is to analyze the job satisfaction status and influencing factors of grassroots health service personnel after the implementation of the family physician contract system in China.MethodsThe study conducted a cross-sectional survey with 570 FPTMs in three prefecture-level cities in the Shandong Province. Satisfaction was measured using 30 items across seven dimensions. Responses were recorded on a 5-point Likert scale. Descriptive statistical analysis was used to analyze the general information and satisfaction of FPTMs. Multiple linear regression analysis was used to analyze the factors influencing job satisfaction.ResultsThe overall job satisfaction among FPTMs was not high. Among the seven dimensions, interpersonal relationships had the highest satisfaction (4.10 ± 0.78), while workload had the lowest satisfaction (3.08 ± 0.56). The satisfaction levels of the three sample regions were different, and the results were opposite to their regional economic development levels. The results of the multifactor analysis showed that gender, income level, educational background, working years, daily working hours, number of training sessions per year and the proportion of performance pay had significant impact on overall job satisfaction.ConclusionsThe development of a family physician contract system has increased the workload of FPTMs. In addition to the implementation of the new policy, attention should be paid to the workload and working attitude of family physicians. The fundamental measures should focus on attracting more personnel to work at the grassroots level by accelerating education and training to solve the problem of insufficient health personnel at the grassroots level. Simultaneously, attention should be paid to the improvement of the medical staff's salary level and the need for self-promotion, such as training.

The purpose was to assess the profile of subconjunctival oblique limbus incision (SCOLI) design by using anterior-segment optical coherence tomography (AS-OCT) and try to emphasize the proper technique of wound construction. The structural dimensions and integrity of the wound were acquired from the patients, who had undergone manual small-incision cataract surgery with SCOLI techniques, using a Canon OCT anterior-segment imaging system on the first postoperative day. The use of AS-OCT allowed for an in vivo evaluation of SCOLI in high definition. The radial OCT scan image showed three staggered incisions, including conjunctiva incision, scleral entrance, and inner corneal lip. A tangential scan demonstrated that the internal lip is parallel to the curvature of the peripheral cornea. The en face image showed an asymmetric 4 arc-shaped configuration rather than a symmetrical one. In conclusion, AS-OCT could be used to analyze SCOLI to determine optimal wound construction and geometry. The results of this study indicated that an asymmetric 4 arc-shaped limbus tunnel incision was superior to the conventional linear equivalent in stability and nucleus delivery.

We have entered an era of population aging, and many public health problems associated with aging are becoming more serious. Older adults have earlier onset of chronic diseases and suffer more disability. Therefore, it is extremely important to promote active aging and enhance health literacy. These involves full consideration of the need for education and the provision of solutions to problems associated with aging. The development of OAE is an important measure for implementing the strategy of active aging, and curriculum construction is a fundamental component of achieving OAE. Various subjective and objective factors have limited the development of OAE. To overcome these difficulties and ensure both active and healthy aging, the requirements for active aging should be implemented, the limitations of current OAE should be addressed, system integration should be increased, and the curriculum system should be improved. These approaches will help to achieve the goal of active aging. This paper discusses OAE from the perspective of active aging, based on the promotion of health literacy and provides suggestions to protect physical and mental health among older adults, while promoting their social participation. The provision of various social guarantees for normal life in older adults is a new educational concept.

BackgroundTumor immunological heterogeneity potentially influences the prognostic disparities among patients with clear cell renal cell carcinoma (ccRCC); however, there is a lack of macroscopic imaging tools that can be used to predict immune-related gene expression in ccRCC.MethodsA novel non-invasive radiogenomics biomarker was constructed for immune-related gene expression in ccRCC. First, 520 ccRCC transcriptomic datasets from The Cancer Genome Atlas (TCGA) were analyzed using a non-negative matrix decomposition (NMF) clustering to identify immune-related molecular subtypes. Immune-related prognostic genes were analyzed through Cox regression and Gene Set Enrichment Analysis (GSEA). We then built a risk model based on an immune-related gene subset to predict prognosis in patients with ccRCC. CT images corresponding to the ccRCC patients in The Cancer Imaging Archive (TCIA) database were used to extract radiomic features. To stratify immune-related gene expression levels, extracted radiogenomics features were identified according to standard consecutive steps. A nomogram was built to combine radiogenomics and clinicopathological information through multivariate logistic regression to further enhance the radiogenomics model. Mann–Whitney U test and ROC curves were used to assess the effectiveness of the radiogenomics marker.ResultsNMF methods successfully clustered patients into diverse subtypes according to gene expression levels in the tumor microenvironment (TME). The relative abundance of 10 immune cell populations in each tissue was also analyzed. The immune-related genomic signature (consisting of eight genes) of the tumor was shown to be significantly associated with survival in patients with ccRCC in TCGA database. The immune-related genomic signature was delineated by grouping the signature expression as either low- or high-risk. Using TCIA database, we constructed a radiogenomics biomarker consisting of 11 radiomic features that were optimal predictors of immune-related gene signature expression levels, which demonstrated AUC (area under the ROC curve) values of 0.76 and 0.72 in the training and validation groups, respectively. The nomogram built by combining radiomics and clinical pathological information could further improve the predictive efficacy of the radiogenomics model (AUC = 0.81, 074).ConclusionsThe novel prognostic radiogenomics biomarker achieved excellent correlation with the immune-related gene expression status of patients with ccRCC and could successfully stratify the survival status of patients in TCGA database. It is anticipated that this work will assist in selecting precise clinical treatment strategies. This study may also lead to precise theranostics for patients with ccRCC in the future.

BackgroundDue to an increasing aging population, China has experienced a rapid expansion in its internal older migrant population who face greater health risks and who have a relatively high demand for health education. Public health education is an important means of preventing diseases and promoting health. However, many studies have focused on the utilization, with few studies examining the impact of public health education on the health of the older migrant population in China.ObjectivesThis study analyzed the impact of public health education on the health of the older migrant population in China.MethodsBased on data obtained from the National Migrant Population Health and Family Planning Dynamic Monitor Survey (2018), logistic models and propensity score matching were used to analyze the impact of public health education on the health of the older migrant population.ResultsThe self-assessed health of China's older migrant population was good, and the acceptance rate of public health education was 40.81%. The public health status of the older migrant population receiving public health education significantly improved (p < 0.05). After correcting for endogeneity among the variables, public health education increased the probability of improving the older migrant population's self-assessed health by 5.4–6.1% (p < 0.01). Heterogeneity analysis found that public health education had a greater impact on the health of older men with an education level of middle school and below, and especially on the older migrant population in the eastern region of China.ConclusionsPublic health education positively affected the health status of the older migrant population. The characteristics and preferences of the older migrant population involving different genders, regions, and educational levels need to be considered, public health education needs to be standardized, and appropriate education methods need to be adopted that suit the older migrant population. Reference suggestions are provided for improving the health level of the older migrant population.

Exosomes are well-known key mediators of intercellular communication and contribute to various physiological and pathological processes. Their biogenesis involves four key steps, including cargo sorting, MVB formation and maturation, transport of MVBs, and MVB fusion with the plasma membrane. Each process is modulated through the competition or coordination of multiple mechanisms, whereby diverse repertoires of molecular cargos are sorted into distinct subpopulations of exosomes, resulting in the high heterogeneity of exosomes. Intriguingly, cancer cells exploit various strategies, such as aberrant gene expression, posttranslational modifications, and altered signaling pathways, to regulate the biogenesis, composition, and eventually functions of exosomes to promote cancer progression. Therefore, exosome biogenesis-targeted therapy is being actively explored. In this review, we systematically summarize recent progress in understanding the machinery of exosome biogenesis and how it is regulated in the context of cancer. In particular, we highlight pharmacological targeting of exosome biogenesis as a promising cancer therapeutic strategy.

Sleep-related breathing disorder (SRBD) is a sleep disease with high incidence and many complications. However, patients are often unaware of their sickness. Therefore, SRBD harms health seriously. At present, home SRBD monitoring equipment is a popular research topic to help people get aware of their health conditions. This article fully compares recent state-of-art research results about home SRBD monitors to clarify the advantages and limitations of various sensing techniques. Furthermore, the direction of future research and commercialization is pointed out. According to the system design, novel home SRBD monitors can be divided into two types: wearable and unconstrained. The two types of monitors have their own advantages and disadvantages. The wearable devices are simple and portable, but they are not comfortable and durable enough. Meanwhile, the unconstrained devices are more unobtrusive and comfortable, but the supporting algorithms are complex to develop. At present, researches are mainly focused on system design and performance evaluation, while high performance algorithm and large-scale clinical trial need further research. This article can help researchers understand state-of-art research progresses on SRBD monitoring quickly and comprehensively and inspire their research and innovation ideas. Additionally, this article also summarizes the existing commercial sleep respiratory monitors, so as to promote the commercialization of novel home SRBD monitors that are still under research.睡眠呼吸障碍（SRBD）是一种睡眠疾病，其患病率高、并发症多，但病情不易察觉，严重危害人体健康。目前，家用SRBD监测设备是领域内的研究热点之一，以提高患者对病情的认识和关注。本文针对SRBD的家庭监护领域，横向对比了近年来的前沿研究成果，旨在全面分析各类技术的优势和局限性，并指明未来研究方向和商业化方向。根据系统设计，可以将新型家用SRBD监护设备划分为可穿戴型和无约束型两类。两类设备各有优劣，可穿戴设备相对简单、便携，但舒适度和续航性能有待提升；而无约束设备则更隐蔽、舒适，但分析算法较为复杂。目前，领域内的研究主要集中在系统设计和性能测试上，但算法优化和临床试验的工作仍有待推进。本文可以帮助科研人员快速而全面地把握领域内的科研进展，从而拓宽科研思路，寻求未来研究的突破点和创新点。此外，本文也归纳了现有的商业化睡眠监护产品，并展望新型家用SRBD监护设备的商业潜力，力图推动科研成果的转化落地。.

The development of rural tourism (RT) has great significance in reducing poverty and achieving rural vitalization. Qinghai-Tibetan Plateau (QTP) is a depressed area with rich RT resources due to its unspoiled nature and diverse culture. For future sustainable development of RT in QTP, this paper analyzes the spatial distribution characteristics and its influencing factors of RT villages using various spatial analysis methods, such as nearest neighbor index, kernel density estimation, vector buffer analysis, and geographic detectors. The results show the following. First, the RT villages present an agglomeration distribution tendency dense in the southeast and spare in the northwest. The inter-county imbalance distribution feature is obvious and four relatively high-density zones have been formed. Second, the RT villages have significant positive spatial autocorrelation, and the area of cold spots is larger and of hot spots is smaller. Third, the RT villages are mainly distributed with favorable topographic and climate conditions, near the road and water, around the city, and close to tourism resources. Fourth, the spatial distribution is the result of multifactor interactions. Socio-economic and tourism resource are the dominant factor in the mechanism network. Fifth, based on the above conclusions this study provides scientific suggestions for the sustainable development of the RT industry.

Due to the rapid growth in sleep medicine's professional content, several countries have recognized sleep medicine as an independent specialty. The practice of sleep medicine and the demand for this service in Asian countries are expanding. At this point of growth, the accreditation of sleep medicine specialists is paramount to patient care and the training of physicians and technologists. The Asian Society of Sleep Medicine (ASSM) mandated a taskforce committee for the accreditation of sleep medicine practice. This taskforce developed Asian accreditation practice guidelines for sleep medicine physicians and technologists. This paper presents the newly approved Asian accreditation practice guidelines for sleep medicine physicians and technologists by the ASSM.

To evaluate the utility of a contact-free device in screening for obstructive sleep apnea.Three hundred fifty-nine participants (mean age 46 ± 13 years, body mass index 26.1 ± 4.2 kg/m², 67.7% male) underwent overnight monitoring using a contact-free device, the OrbSense, and polysomnography (PSG) in the sleep laboratory simultaneously. The OrbSense recordings were analyzed automatically, and PSG was scored based on recommended guidelines.The respiratory event index from the OrbSense was lower than the apnea-hypopnea index (AHI) from PSG (25.5 ± 20.7 vs 27.0 ± 25.2 events/h; P = .007) and was significantly correlated with AHI (Pearson coefficient, 0.92; P.0001). Bland-Altman analysis showed a mean difference of 1.5 events/h, and the limit of agreement was -18.6 to 21.5 events/h. Use of the OrbSense resulted in larger underestimates of AHI and lower negative predictive values at higher AHI values (especially when AHI ≥ 30 events/h). When we used a PSG diagnostic criterion of AHI5 events/h, the optimal diagnostic cutoff value from the OrbSense was 8 events/h, with a sensitivity of 90.4%, a specificity of 77.6%, a 94.6% positive predictive value, and a 65% negative predictive value. For patients with moderate to severe obstructive sleep apnea whose AHI was15 events/h, the OrbSense cutoff was 16.6 events/h, with a sensitivity of 87.1% and a specificity of 89.7%. Among the 359 participants, 250 patients (69.6%) had the same obstructive sleep apnea severity division classified by both PSG and the OrbSense.The contact-free device OrbSense can detect respiratory events during sleep and has close agreement with in-laboratory PSG in screening for obstructive sleep apnea. Further studies are warranted to test its utility in community-based settings and at home.

Background Major depressive disorder (MDD) is a multifaceted mental disorder where participants, in addition to various symptoms, often suffer from increased focus on past time perspective and higher incidence of childhood trauma. Whether the abnormal time perspective is a result of the depressive symptoms or, alternatively, mediates between childhood trauma and depression remains unclear. Aims To examine the triangular relationship between early life trauma, time perspective, and depressive symptoms. Method We investigated a large-scale MDD sample (n = 93) and healthy subject sample (n = 69) with Beck depression inventory-II (BDI-II), Beck hopelessness scale (BHS), childhood traumatic questionnaire-Short Form (CTQ-SF), and the Zimbardo time perspective inventory (ZTPI). Results The MDD patients reported more childhood trauma experiences, and were featured by abnormal time perspectives on past and future when compared to healthy control. By applying two alternative mediation models, we observed that the time perspective acted as a mediator between childhood trauma and depressive symptom severity, rather than as a consequence of depressive symptom. Furthermore, this abnormal time perspective was a risk factor to MDD, as the childhood trauma only mediated the time perspective in MDD. Finally, we showed that time perspective was a long-term personal trait and unchanged after the remission of depression symptoms under five-day transcranial magnetic stimulation. Conclusions Abnormal time perspective mediates the impact of early childhood trauma on depressive symptomatology. Besides better understanding of the temporal basis of depressive symptoms, we highlight the importance of preventive time perspective therapy in subjects with childhood trauma.

Previous studies reported that ferroptosis-related genes can regulate the process of tumor cell changes by regulating iron metabolism. However, the prognostic value of ferroptosis-related genes in LC remains to be further elucidated. Ferroptosis-related gene expression profiles of coexisting ferroptosis-related genes were extracted from both cohorts (TCGA and GSE27020) for eligible analysis. LASSO Cox regression was utilized to build an optimum ferroptosis-related prognostic model. Kaplan–Meier curve was performed by log‐rank test, and time‐dependent ROC curve was constructed to evaluate the predictive power of this signature in both cohorts. GO and KEGG enrichment analysis was used to investigate the potential mechanism of differential enrichment signal pathways. 112 LC patients from the TCGA cohort and 108 LC patients with clinical information from the GEO cohorts were eventually included in the study. Three ferroptosis-related genes were identified as an independent risk factor to establish the prognostic risk score. Kaplan–Meier curve represented that patients with high-risk group favors with worse OS than their low-risk group (P = 0.04). The good performance of the gene signature for predicting OS was evaluated by area under the curve (AUC) of time-dependent ROC curves achieved 0.74 at 3 years, and 0.70 at 5 years. Similar performance has been proved in the external validation cohort. GO and KEGG enrichment analysis have been performed to explore the signaling pathways and underlying mechanisms were significantly active in LC patients. In summary, our study developed a ferroptosis-related model that could be an effective biomarker to predict the prognosis of laryngeal cancer.

Gallium-based liquid metal droplets (LMDs) from micro-electromechanical systems (MEMS) have gained much attention due to their precise and sensitive controllability under an electric field. Considerable research progress has been made in the field of actuators by taking advantage of the continuous electrowetting (CEW) present within the solution. However, the motion generated is confined within the specific liquid environment and is lacking a way to transmit its motion outwardly, which undoubtedly serves as the greatest obstacle restricting any further development. Therefore, a driving module is proposed to generate rotational motion outside the solution for universality. Its performance can be easily tuned by adjusting the applied voltage. As an example of further application, the module is designed in the form of a pump that realizes the continuous/intermittent propulsion to mimic the veins/arteries of the human body without the problem in the previous LMD-based pumps. The feasibility of this pump in the on-chip in vitro analysis is proved by preparing a dynamic cell culture to simulate the movement of biofluids within human bodies. This study proposes an optional solution with an LMD-based motor for generating rotational motion and to expand current research on soft materials in actuators.

Fungal keratitis (FK) is a serious corneal infection caused by pathogenic fungi. Monocyte chemoattractant protein-induced protein 1 (MCPIP1) plays an important role in restricting the inflammatory response in various immune disorders. However, the function of MCPIP1 in Aspergillus fumigatus (A. fumigatus) keratitis is unclear. In the present study, we found that A. fumigatus infection promotes the expression of MCPIP1 in human corneal epithelial cells (HCECs) and in mouse corneas. Overexpression of MCPIP1 decreased the production of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, while knockdown of MCPIP1 increased the expression of these cytokines. MCPIP1 enhanced autophagy flux by inhibiting the mTOR signaling in HCECs with A. fumigatus infection. Further study showed that inhibition of autophagy using chloroquine reverses the anti-inflammatory effect of MCPIP1 in HCECs infected with A. fumigatus. Moreover, MCPIP1 alleviated the severity of keratitis and inhibited the expression of inflammatory cytokines by activating autophagy in an FK mouse model. In conclusion, our study demonstrated that MCPIP1 alleviates the severity of A. fumigatus keratitis by inducing mTOR-mediated autophagy in HCECs and in a mouse model. Exogenous use of MCPIP1 protein may have potential applications in FK clinical therapy.

PurposeTo evaluate capillaries perfusion and retinal nerve fiber layer (RNFL) thickness diurnal changes of macular/optic disc regions among participants with or without obstructive sleep apnea-hypopnea (OSA) using spectral-domain optical coherence tomography angiography (OCTA).MethodsIn this study, we enrolled a cohort of 35 participants including 14 patients with mild-to-moderate OSA, 12 patients with severe OSA, and 9 healthy individuals. All participants had Berlin questionnaire filled. At 20:00 and 6:30, right before and after the polysomnography examination, a comprehensive ocular examination was conducted. The systemic and ocular clinical characteristics were collected, and OCTA scans were performed repeatedly. Blood flow and RNFL thickness parameters were then exported using built-in software and analyzed accordingly.ResultsAfter sleep, the overall vessel density (VD) variables, especially macular and choriocapillaris VDs, were relatively comparative and stable. One exception was the RPC vessel density at the inside-disc region with a decreasing trend in the mild-to-moderate group (p=0.023). RNFL changes before and after sleep in the nasal-inferior and peripapillary region were statistically significant (p=0.003; p=0.043) among three groups. And multiple testing correction verified the significant difference in diurnal changes between the mild-to-moderate group and the control group in pairwise comparisons (p=0.006; p=0.02).ConclusionsThe changes of imperceptible blood flow and RNFL thickness overnight around optic disc areas could be observed in OSA patients. Despite physiological fluctuations, aberrant diurnal changes might be useful for identifying a decrease in micro-environmental stability associated with the development of various ocular diseases such as glaucoma. Other VD variables, especially macular and choriocapillaris VDs, are relatively stable in eyes of patients having OSA with different severity.

During the pandemic, the mortality salience of COVID-19 has affected everyone. The public is extremely sensitive to food safety, especially cold chain food and imported food. This research is based on the terror management theory, protective motivation theory, and self-construal theory. It proposes an integrated dual-path framework to explore the different mechanisms that mortality salience has on food safety behavior. The result of three experiments verified our conjectures. First, mortality salience positively affects individuals’ food safety behavior. More importantly, we found the dual-path mechanism that underlies the effect, that is, the mediating of self-protective motivation and prosocial motivation. In addition, different self-construals make the confirmed effect clear. These findings provide implications for the government to protect public food safety and health.

Nature-based recreation (NBR) is an important cultural ecosystem service providing human well-being from natural environments. As the most concentrated and high-quality wilderness in China, the Qinghai-Tibet Plateau (QTP) has unique advantages for NBR. In this study, we designed an integrated nature-based recreation potential index (INRPI) based on four aspects: nature-based recreation resources, landscape attractiveness, recreation comfort and opportunity, and recreation reception ability. A combination of the analytic hierarchy process (AHP) and entropy evaluation method was adopted to assess the NBR potential in the QTP from 2000 to 2020. The research shows that: (i) The INRPI for the QTP decreases gradually from southeast to northwest and increases slightly from 2000 to 2020. (ii) The INRPI displays a pronounced difference on either side of the Qilian-Gyirong line. The areas with very high and high potentials mainly distributed in the southeast of the line, while areas with very low and low potentials distributed in the northwest. (iii) The construction of protected areas effectively improves NBR potential. Areas of INRPI at diverse levels within protected areas obviously increased in 2020. (iv) Increasing altitude has a notable effect on INRPI, and 3000 m is a critical dividing line for the NBR in the QTP. These findings can contribute to decision-makers in guiding rational use and spatial planning of natural land and promoting sustainable recreational development.

Objectives To assess perinatal outcomes of COVID-19 infections during pregnancy and the possibility of vertical transmission. Methods An analysis was performed using Stata 15.0, and Q-test was used to evaluate the heterogeneity of the included studies. Results The most common symptoms were found to be fever (64.78%), cough (59.81%) and shortness of breath or dyspnea (23.86%). Of this 88.73% patients demonstrated typical COVID-19 signs on chest CT or X-ray. Intubation was carried out in 35.87% of patients, and 4.95% of mothers were admitted to the intensive care unit, where the rate of maternal death was Conclusions Pregnant patients with COVID-19 most commonly presented with fever, cough, shortness of breath and dyspnea, most of which possessed imaging manifestations. The risk of intubation and admission to intensive care unit were high. The risk of premature delivery was higher, leading to a high risk of NICU admission and low neonatal birthweight. Vertical transmission of SARS-CoV-2 from mother to child was found to be unlikely.

To compare capillaries perfusion in macular areas at different layers and peripapillary region in radial peripapillary capillaries (RPC) between healthy subjects and subjects with obstructive sleep apnea–hypopnea (OSA) using spectral-domain optical coherence tomography angiography (OCTA). Totally 16 eyes with mild-to-moderate OSA, 14 eyes with severe OSA and 22 control eyes were enrolled in this study. Every subject filled out the Berlin questionnaire and received a comprehensive ocular and physical examination. The clinical characteristics were collected, OCT and OCTA scans using OCTA RT XR Avanti (AngioVue software, Optovue Inc., Fremont, CA, USA) were performed and analyzed. Compared to the control group, the severe group had significantly higher VD in parafovea and perifoveal regions (p = 0.031; p = 0.029) at the level of deep capillary plexus (DCP), whereas the mild-to-moderate group had a significantly lower VD in the peripapillary region on RPC network in disc areas (p = 0.013). Blood flow changes in macular areas might first appear at the DCP layer in OSA patients. Reduced VD in the peripapillary region at the RPC layer might be associated with OSA and cause subsequent RNFL changes.

Background Narcolepsy type 1 (NT1) is considered to be an autoimmune disease, and streptococcal infection may be an environmental trigger. However, previous studies from Asian narcolepsy patients did not reveal elevated anti-streptolysin O [ASO]. The aim is to investigate whether large sample Chinese patients with NT1 have an increase in antistreptococcal antibody titers. Methods A total of 214 narcolepsy patients and 360 healthy controls were recruited. All patients were DQB1∗0602 positive with clear-cut cataplexy or had low CSF hypocretin-1. Participants were tested for ASO and anti DNAse B [ADB]. These patients were divided into five groups according to disease duration, including 29 patients less than 3 months; 25 from 3 months to 1 year; 40 from 1 to 3 years; 61 from 3 to 10 years and 59 patients over 10 years. Comparison was also made between children and adults with age matched controls, respectively. Results There were no significant differences between patients and healthy controls in regard to both ASO ≥200 IU (19.2% vs. 16.9%, p = 0.50) and ADB≥480IU (9.8% vs. 10.3%, p = 0.86). For children narcolepsy patients, ASO positive rates (19.8% vs. 18%, p = 0.68) and ADB positive rates (10.4% vs. 12%, p = 0.72) had no differences compared to age matched controls. No difference was observed in adult narcolepsy patients either, with ASO positive rates (18.5% vs. 13.8%, p = 0.39) and ADB positive rates (9.3% vs. 5.3%, p = 0.42) compared to age matched controls, respectively. ASO and ADB positive rates had no significant differences among different disease duration groups (p = 0.55 and 0.9, respectively). Conclusion Streptococcus infection reflected by increase of ASO and ADB levels was not found in Chinese patients with type 1 narcolepsy, additional triggers for narcolepsy need to be addressed in this population.

BackgroundPostoperative pain in ambulatory surgery is a multifactorial issue affecting patient satisfaction, time of discharge, and rehospitalization. This study evaluated the efficacy and safety of nalbuphine for the treatment of postoperative pain after ambulatory surgery, relative to tramadol.MethodsThis multi-center, randomized, double blind, and controlled study was conducted at 10 centers. In accordance with the inclusion criteria, 492 ambulatory surgery patients were recruited. These patients had moderate to severe pain after ambulatory surgery, with a visual analogue scale (VAS) score > 3 cm. They were randomly divided into an experimental (n = 248) or control (n = 244) group and treated for analgesia with 0.2 mg/kg of nalbuphine or 2 mg/kg of tramadol, respectively. VAS scores, adverse events, and vital signs of the patients were recorded before administration (baseline; T1); and 30 min (T2), 2 h (T3), 4 h (T4), and 6 h (T5) after administration of analgesia. A decrease in pain intensity of more than 25% compared with the baseline was used as an indicator of analgesic efficacy. The experimental and control groups were compared with regard to this indicator of efficacy at each timepoint.ResultsThe VAS scores of the experimental and control groups were statistically comparable at timepoints T1-T4. At T5, the VAS scores of the experimental group were significantly lower than that of the control. The pain intensity was significantly higher in the experimental group compared with the control at T2and T3. Adverse events and vital signs were similar for the two groups at each timepoint.ConclusionsNalbuphine can provide effective and safe pain relief in patients after ambulatory surgery.Trial registrationThe registration number isChiCTR-IOR-16010032, the date of registration was 2016-11-28.

Background Postoperative pulmonary complications (PPCs) are common and significant problems for oral and maxillofacial surgery patients. Dexmedetomidine (DEX), an α2-adrenoreceptor agonist, has been proven having lung protection effects. However, since now, there has not been final conclusion about whether DEX can reduce the incidence of PPCs. We hypothesize that, in oral and maxillofacial surgery with fibular free flap reconstruction patients, DEX may decrease the incidence of PPCs. Methods This was a prospective, double-blind, randomized, placebo-controlled, single-centered trial with two parallel arms. A total of 160 patients at intermediate-to-high risk of PPCs undergoing oral and maxillofacial surgery with fibular free flap reconstruction and tracheotomy were enrolled and randomized to receive continuous infusion of either DEX or placebo (normal saline). 0.4 μg/kg of DEX was given over 10mins as an initial dose followed by a maintaining dose of 0.4 μg/kg/h till the second day morning after surgery. At the same time, the normal saline was administered a similar quantity. The primary outcome was the incidence of PPCs according to Clavien-Dindo score within 7 days after surgery. Results The two groups had similar characteristics at baseline. 18(22.5%) of 80 patients administered DEX, and 32(40.0%) of 80 patient administered placebo experienced PPCs within the first 7 days after surgery (relative risk [RR] 0.563,95% confidence interval [CI] 0.346–0.916; P = 0.017). In the first 7 days after surgery, the DEX group had a lower incidence of PPCs and a better postoperative survival probability (Log-rank test, P = 0.019), and was less prone to occur PPCs (Cox regression, P = 0.025, HR = 0.516). When the total dose of DEX was more than 328 μg, the patients were unlikely to have PPCs (ROC curve, AUC = 0.614, P = 0.009). Conclusions For patients undergoing oral and maxillofacial surgery with fibular free flap reconstruction and tracheotomy who were at intermediate or high risk of developing PPCs, continuous infusion of DEX could decrease the occurrence of PPCs during the first 7 days after surgery and shorten the length of hospital stay after surgery, but did not increase the prevalence of bradycardia or hypotension. Trial registration Chinese Clinical Trial Registry, www.chictr.org.cn, number: ChiCTR1800016153; Registered on May 15, 2018.

Post-traumatic stress disorder (PTSD) patients exhibit abnormal learning and memory. Axons from orexin neurons in the lateral hypothalamus innervate the hippocampus, modulating learning and memory via the orexin 1 and 2 receptors (OX1R and OX2R). However, the role of the orexin system in the learning and memory dysfunction observed in PTSD is unknown. This was investigated in the present study using PTSD animal model-single prolonged stress (SPS) rats. Spatial learning and memory in the rats were evaluated with the Morris water maze (MWM) test; changes in body weight and food intake were recorded to assess changes in appetite; and the expression of orexin-A and its receptors in the hypothalamus and hippocampus was examined and quantified by immunohistochemistry, western blotting and real-time PCR. The results showed that spatial memory was impaired and food intake was decreased in SPS rats; this was accompanied by downregulation of orexin-A in the hypothalamus and upregulation of OX1R and OX2R in the hippocampus and of OX1R in the hypothalamus. Intracerebroventricular administration of orexin-A improved spatial memory and enhanced appetite in SPS rats and partly reversed the increases in OX1R and OX2R levels in the hippocampus and hypothalamus. These results suggest that the orexin system plays a critical role in the memory and appetite dysfunction observed in PTSD.

Objective. To investigate the clinical study of intravitreal injection of anti-VEGF drugs combined with intravitreal injection of tretinoin for the treatment of Coats disease. Methods. The medical records of 90 patients (120 eyes) with Coats disease admitted to our hospital from April 2010 to June 2021 were selected as retrospective study subjects and divided into control and treatment groups according to the numerical table method. There were 45 cases and 60 eyes in each group. Among them, intravitreal tretinoin drug was injected into the control group, and anti-VEGF drug was injected into the vitreous sclera of the treatment group on the basis of the control group. Results. Before treatment, the differences in visual acuity changes between the two groups were not statistically significant ( P > 0.05 ). After treatment, the light perception, manipulation, and indexes of both groups were significantly improved, and the treatment group was significantly better than the control group. This difference was statistically significant ( P < 0.05 ) for statistical study comparison. The effective rate of 95.56% in the treatment group was significantly higher than that of 86.67% in the control group, and the complication rate was significantly lower than that of the control group, with statistically significant differences ( P < 0.05 ). Conclusion. Intravitreal injection of anti-VEGF drugs combined with tretinoin injection can significantly improve the clinical efficacy of patients with Coats disease and improve visual acuity and central retinal thickness, which has certain reference value for the clinical treatment of Coats disease.

Obstructive Sleep Apnea (OSA) is a disorder that is characterized by obstructive apneas and hypopneas/respiratory effort-related arousals caused by upper airway collapse during sleep. Positive Airway Pressure (PAP) is the first-line treatment for moderate to severe OSA. However, the effectiveness of PAP therapies is contingent on treatment adherence. With the implementation of the wireless transmission for PAP treatment, it is possible to evaluate the objective adherence to PAP use. The purpose of this study is to assess the adherence to PAP therapy of Chinese OSA patients in a telemedicine management system which could fulfill automatic transmission of PAP treatment data. First, we use the telemedicine management system to extract PAP adherence information of OSA adult patients in one week, one month, three months, six months and 12 months. Second, we describe the general profile of PAP therapy adherence. Third, the latent class growth modeling and growth mixture modeling was conducted using Mplus 8.0 to identify the trajectories of adherence over time. Of all the 662 patients involved in our study, PAP adherence declined over time. After one year, the proportion of days compliant was 53.7%, the proportion of good compliance was 45.2%, the daily usage (all days) was 3.9 h/night, slightly lower than subjective adherence reported in the previous literatures. In addition, we identified three patterns of adherence over time: great users (39.9%; high mean value and level, negative slope, slow decline), good users (34.8%; moderate mean value and level, negative slope, rapid decline) and low users (25.3%; low mean value and level, negative slope, rapid decline). In brief, telemedicine management system provides a convenient platform for monitoring the treatment compliance of OSA patients powerfully and accurately. To improve the low PAP adherence in China, we should make good use of the PAP therapy telemedicine management platform to detect patients with poor adherence and provide timely intervention. Besides, our research provides a foundation for future studies to explore the determinants of observed trajectories of PAP adherence based on the telemedicine platforms.

To investigate the prevalence of core attention-deficit/hyperactivity disorder (ADHD) symptoms in Chinese narcolepsy type 1 (NT1) patients and to explore mood, quality of life, and executive function in narcolepsy patients with or without ADHD and the response to Methylphenidate Hydrochloride Extended-release tablets (ER-MPH) treatment.A total of 267 pediatric NT1 patients (194 males and 73 females, 5-17 years old) were evaluated for ADHD symptoms by a psychiatrist using the DSM-IV diagnostic criteria of the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI Kid) from February 2011 to July 2013 at Peking University People's Hospital. All patients underwent Stanford Sleep Inventory (SSI) evaluation and polysomnography followed by multiple sleep latency tests (MSLT) before ER-MPH treatment. Neuropsychological evaluations, including the Inventory of Subjective Life Quality (ISLQ), Depression Self-resting Scale for Children (DSRS-C), Screening for Child Anxiety-related Emotional Disorders (SCARED) and Barratt Impulsiveness Scale (BIS), were performed before and after 16 weeks of ER-MPH treatment. Executive abilities were assessed by the Behavior Rating Inventory of Executive Function-parent version (BRIEF-P). The narcolepsy symptoms, evaluated by the Pediatric Sleep Questionnaire (PSQ), and ADHD symptoms were assessed before and after treatment in NT1 patients with ADHD.Seventy-seven of 267 (28.8%) NT1 patients had ADHD symptoms, with 73 patients being inattentive type (ADHD-I) and 4 patients being combined type (ADHD-C). Despite similar objective sleep parameters, NT1 patients with ADHD symptoms experienced higher anxiety levels, more impulsive behaviors, lower health-related quality of life and worse executive functions than those without ADHD (p0.05). Methylphenidate treatment was effective in improving daytime sleepiness in NT1 patients with ADHD (PSQ, 16.7 ± 2.1 vs 13.5 ± 1.9, p0.05) but was ineffective on ADHD symptoms (ADHD-RS, 25.3 ± 9.1 vs 26.4 ± 8.9, p0.05).A high prevalence of ADHD (28.8%) was identified in children and adolescents with NT1. Comorbid ADHD symptoms were associated with increased levels of mood disorders and lower quality of life. ER-MPH treatment could reduce daytime sleepiness but not ADHD symptoms in narcolepsy patients with ADHD, suggesting that new treatment strategies are needed for this group of patients.

Thyroid cancer is the most prevalent endocrine malignancy and the reported incidence of thyroid cancer has continued to increase in recent years. Since 2019, coronavirus disease 2019 (COVID-19) has been spreading worldwide in a global pandemic. COVID-19 aggravates primary illnesses and affects disease management; relevant changes include delayed diagnosis and treatment. The thyroid is an endocrine organ that is susceptible to autoimmune attack; thus, thyroid cancer after COVID-19 has gradually attracted attention. Whether COVID-19 affects the diagnosis and treatment of thyroid cancer has also attracted the attention of many researchers. This review examines the literature regarding the influence of COVID-19 on the pathogenesis, diagnosis, and treatment of thyroid cancer; it also focuses on drug therapies to promote research into strategies for improving therapy and management in thyroid cancer patients with COVID-19.

Resistance to PARP inhibitors (PARPi) remains a therapeutic challenge in ovarian cancer patients. PDZ-binding kinase (PBK) participates in the chemoresistance of many malignancies. However, the role of PBK in PARPi resistance of ovarian cancer is obscure. In the current study, we demonstrated that overexpression of PBK contributed to olaparib resistance in ovarian cancer cells. Knockdown of PBK sensitized olaparib-resistant SKOV3 cells to olaparib. Inhibition of PBK using a specific inhibitor enhanced the therapeutic efficiency of olaparib. Mechanically, PBK directly interacted with TRIM37 to promote its phosphorylation and nuclear translocation. which subsequently activates the NFκB pathway. Additionally, PBK enhanced olaparib resistance of ovarian cancer by regulating the NFκB/TRIM37 axis in vitro and in vivo. In conclusion, PBK confers ovarian cancer resistance to PARPi through activating the TRIM37-mediated NFκB pathway, and targeted inhibition of PBK provided the new therapy to improve PARPi treatment outcomes for ovarian cancer patients.

We consider an increasingly popular study design where single-cell RNA-seq data are collected from multiple individuals and the question of interest is to find genes that are differentially expressed between two groups of individuals. Towards this end, we propose a statistical method named IDEAS (individual level differential expression analysis for scRNA-seq). For each gene, IDEAS summarizes its expression in each individual by a distribution and then assesses whether these individual-specific distributions are different between two groups of individuals. We apply IDEAS to assess gene expression differences of autism patients versus controls and COVID-19 patients with mild versus severe symptoms. Supplementary Information The online version contains supplementary material available at (10.1186/s13059-022-02605-1).

Microglia are known to play essential roles in the development, progression and treatment of diverse neurodegenerative diseases in the central nervous system, including the retina, brain and spinal cord. Recently, brain-induced microglia-like cells (iMGs) have been generated from human pluripotent stem cells (hPSCs); however, retinal microglia have yet to be developed in vitro. In this study, by mimicking in vivo microglial development, we established a simplified approach to differentiate hPSCs into high purity (90%) iMGs. The iMGs express microglia-specific markers, release cytokines upon stimulation, and are capable of phagocytizing bacteria. When co-cultured with three-dimensional human retinal organoids (hROs), iMGs migrated into the hROs, tended to differentiate into resident retinal microglia, and simultaneously induced apoptosis in some neural cells. Notably, the resident iMGs in the hROs formed sparse web-like structures beneath the photoreceptor cell layer, resembling microglia's orientation in human retina. In conclusion, we developed a simplified and efficient method to generate microglia from human pluripotent stem cells, and we report the first derivation of retinaresident microglia in vitro, providing a new source of human retinal microglia for developmental and disease studies and regenerative therapeutics.

The effectiveness of neoadjuvant therapy (NAT) remains controversial in the treatment of pancreatic cancer (PC). Therefore, this meta-analysis aimed to investigate the clinical differences between NAT and upfront surgery (US) in resectable pancreatic cancer (RPC). Eligible studies were retrieved from PubMed, Embase, and Cochrane Library. The endpoints assessed were R0 resection rate, pathological T stage2 rate, positive lymph node rate, and overall survival. A total of 4,588 potentially relevant studies were identified, and 13 studies were included in this study. In patients with RPC, this meta-analysis showed that NAT presented an increased R0 resection rate, pathological T stage2 rate, and a remarkably reduced positive lymph node rate compared to US. However, patients receiving NAT did not result in a significantly increased overall survival. These findings supported the application of NAT, especially as a patient selection strategy, in the management of RPC. Additional large clinical studies are needed to determine whether NAT is superior to US.

Anticancer therapies with profound efficacy but negligible toxicity are a fundamental pursuit that has been made humanly possible through either targeting or tumor-selective therapeutic (TST) approaches. Herein, we developed a targeting-enhanced tumor-selective cancer therapy aimed at integrating the two approaches by preparing cerium oxide (CeO2) nanocubes with glucose oxidase (GOx) modified on the cube surface and cancer cell membrane (CCM) camouflaged outside. The immune escape and homotypic binding of camouflaged CCM enable targeted delivery of the resultant CeO2-GOx@CCM nanoparticles mostly into cancer tissue, while its acidic environment (pH < 6.6) activated a cascade reaction, in which the glucose was first catalyzed by GOx into H2O2 and then by CeO2 into highly cytotoxic ˙OH killing cancer cells. In the case of off-targeting, when very few CeO2-GOx@CCM nanoparticles were accidentally delivered into normal tissue, its neutral pH environment (pH = 7.4) triggered a protective reaction, in which the H2O2 generated was catalyzed by CeO2 into non-toxic H2O and O2. Both in vitro and in vivo results demonstrated that this targeting-enhanced TST achieved the most remarkable antitumor performance with negligible toxic side effects.

BACKGROUND: Prediction tools without patient-reported symptoms could facilitate widespread identification of OSA. RESEARCH QUESTION: What is the diagnostic performance of OSA prediction tools derived from machine learning using readily available data without patient responses to questionnaires? Also, how do they compare with STOP-BANG, an OSA prediction tool, in clinical and community-based samples? STUDY DESIGN AND METHODS: Logistic regression and machine learning techniques, including artificial neural network (ANN), random forests (RF), and kernel support vector machine, were used to determine the ability of age, sex, BMI, and race to predict OSA status. A retrospective cohort of 17,448 subjects from sleep clinics within the international Sleep Apnea Global Interdisciplinary Consortium (SAGIC) were randomly split into training (n = 10,469) and validation (n = 6,979) sets. Model comparisons were performed by using the area under the receiver-operating curve (AUC). Trained models were compared with the STOP-BANG questionnaire in two prospective testing datasets: an independent clinic-based sample from SAGIC (n = 1,613) and a community-based sample from the Sleep Heart Health Study (n = 5,599). RESULTS: The AUCs (95% CI) of the machine learning models were significantly higher than logistic regression (0.61 [0.60-0.62]) in both the training and validation datasets (ANN, 0.68 [0.66-0.69]; RF, 0.68 [0.67-0.70]; and kernel support vector machine, 0.66 [0.65-0.67]). In the SAGIC testing sample, the ANN (0.70 [0.68-0.72]) and RF (0.70 [0.68-0.73]) models had AUCs similar to those of the STOP-BANG (0.71 [0.68-0.72]). In the Sleep Heart Health Study testing sample, the ANN (0.72 [0.71-0.74]) had AUCs similar to those of STOP-BANG (0.72 [0.70-0.73]). INTERPRETATION: OSA prediction tools using machine learning without patient-reported symptoms provide better diagnostic performance than logistic regression. In clinical and community-based samples, the symptomless ANN tool has diagnostic performance similar to that of a widely used prediction tool that includes patient symptoms. Machine learning-derived algorithms may have utility for widespread identification of OSA.

OBJECTIVE Vigabatrin (VGB) is the first-line treatment for infantile spasms (IS). Previous studies have shown that VGB exposure may cause vigabatrin-associated brain abnormalities on magnetic resonance imaging (MRI) (VABAM). Based on previous studies, this study aimed to go further to explore the possible risk factors and the incidence of VABAM. In addition, diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) were compared to explore whether DWI should be used as a routine examination sequence when MRI is performed in children receiving VGB. METHODS Children with IS receiving VGB were selected as the study subjects. Whether VABAM occurred or not was categorized as the VABAM group and the non-VABAM group, respectively. Their general clinical data and medication exposure were collected. The possible risk factors of VABAM and different MRI sequences were compared and statistically analyzed. RESULTS A total of 77 children with IS were enrolled in the study, of which 25 (32.5%) developed VABAM. Twenty-three of the 25 VABAM cases have a peak dosage of VGB between 50 and 150 mg/kg/day. The earliest observation time of VABAM was 30 days. Regression analysis of relevant risk factors showed that the peak dosage of VGB was the risk factor for VABAM. Comparison between different MRI sequences showed that DWI is more sensitive than T2WI to the evaluation of VABAM. SIGNIFICANCE In our study, the occurrence of VABAM was 32.5%, indicating a higher incidence than in most previous reports. In addition, we once again verified that the peak dosage of VGB was the risk factor of VABAM. Caution should be exercised that our data also suggest that VABAM may occur even using the conventional dosage of VGB (ie, 50-150 mg/kg/day). Therefore, even when using the conventional dosage of VGB, regular MRI examination should be required. Furthermore, DWI sequence should be used as a routine examination sequence when MRI is performed in children with IS who are receiving VGB.

STUDY OBJECTIVES: Catathrenia is a rare disease, classified as isolated symptoms and normal variants under sleep-related breathing disorders in the International Classification of Sleep Disorders, third edition. Because of its rarity, the research on its pathogenesis and treatment is insufficient. This study aimed to evaluate whether the mandibular advancement device (MAD) could be considered an alternative treatment trial and if so, to explore factors predicting its effectiveness. METHODS: Thirty patients (12 men and 18 women, aged 16–67 years) with catathrenia participated in the study. They underwent standard clinical evaluation, questionnaires, physical examinations, craniofacial evaluations, video polysomnography, and imaging of the upper airway before and after the insertion of the MAD. The groaning index (groaning episodes per hour of sleep) and apnea-hypopnea index were evaluated, and anatomic factors predicting effectiveness were explored. RESULTS: The sleep efficiency of most patients was higher than 80%, and groaning was present throughout all stages of sleep. With the insertion of the MAD, the groaning index decreased significantly from 5.8 (2.7–14.3) to 2.8 (1.3–12.2) events/h (P = .014). Age had a negative effect on efficacy. Mandibular repositioning of the MAD, especially the amount of vertical opening and changes of the cross-sectional area of the hypopharynx, was positively related with efficacy. CONCLUSIONS: The MAD could be considered a possible treatment trial for those seeking treatment for groaning. CLINICAL TRIAL REGISTRATION: Registry: Chinese Clinical Trial Register; Name: The etiology of catathrenia based on oral and maxillofacial system; URL: http://www.chictr.org.cn/showproj.aspx?proj=22286; Identifier: ChiCTR-COC-17013239. CITATION: Yu M, Hao Z, Xu L, Wen Y, Han F, Gao X. Mandibular advancement device as treatment trial for catathrenia (nocturnal groaning). J Clin Sleep Med. 2021;17(9):1767–1776.

AimsWe conducted a systematic review and meta-analysis to assess various antidiabetic agents’ association with mortality in patients with type 2 diabetes (T2DM) who have coronavirus disease 2019 (COVID-19).MethodsWe performed comprehensive literature retrieval from the date of inception until February 2, 2021, in medical databases (PubMed, Web of Science, Embase, and Cochrane Library), regarding mortality outcomes in patients with T2DM who have COVID-19. Pooled OR and 95% CI data were used to assess relationships between antidiabetic agents and mortality.ResultsEighteen studies with 17,338 patients were included in the meta-analysis. Metformin (pooled OR, 0.69; P=0.001) and sulfonylurea (pooled OR, 0.80; P=0.016) were associated with lower mortality risk in patients with T2DM who had COVID-19. However, patients with T2DM who had COVID-19 and received insulin exhibited greater mortality (pooled OR, 2.20; P=0.002). Mortality did not significantly differ (pooled OR, 0.72; P=0.057) between DPP-4 inhibitor users and non-users.ConclusionsMetformin and sulfonylurea could be associated with reduced mortality risk in patients with T2DM who have COVID-19. Furthermore, insulin use could be associated with greater mortality, while DPP-4 inhibitor use could not be. The effects of antidiabetic agents in patients with T2DM who have COVID-19 require further exploration.Systematic Review RegistrationPROSPERO (identifier, CRD42021242898).

To evaluate whether sirolimus treatment could relieve the later burden of new-onset seizures in patients with tuberous sclerosis complex (TSC) prior to epilepsy.A real-world matched case-control study was nested in another registry cohort study. Infants with TSC (12 months old) without seizures whose parents agreed on sirolimus treatment for other symptoms were eligible for inclusion to the early sirolimus (ES) group. These patients were enrolled from 2015 to 2018. Controls in the late sirolimus (LS) group were matched from the registry cohort database for 2015-2018. Age and genotype were used as the initial stratifying criteria and other symptoms as the greedy matching criteria at a matching ratio of 1:4. None of the preventive drugs were introduced before seizure onset or before 2 years of age in the LS group. Both groups were followed up until June 2020. The primary objective was a comparison of the characteristics of the first seizure between the two groups. The secondary objective was the assessment of the final seizure status at the endpoint.There were 42 and 168 patients with TSC in the ES and LS groups, respectively. Early sirolimus treatment significantly reduced the seizure onset, especially in the patients aged6 months. The mean onset-age was significantly delayed by sirolimus treatment (11.34±7.93 months vs. 6.94±6.03 months, P0.001). The subtype of seizures that benefited the most was spastic (onset) seizures (all were infantile spasms) [5/42 (11.90%) vs. 73/168 (43.45%), P0.001]; these seizures were either eliminated or alleviated. The sirolimus treatment addition prior to seizures was more effective than its addition after seizures in reducing drug-resistant epilepsy [10/42 (23.81%) vs. 70/147 (47.62%), P=0.004].Early sirolimus treatment for TSC effectively modified the disease by preventing infantile spasms, delaying seizure onset, and relieving its severity. The anti-epileptogenic effect of sirolimus may be time- and dose-dependent.

Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) resistance remains a therapeutic challenge in ovarian cancer. High-mobility group box 3 (HMGB3) plays significant roles in the development of drug resistance of many cancers. However, the function of HMGB3 in PARPi resistance is poorly understood. In the current study, we clarified that HMGB3 was aberrantly overexpressed in high-grade serous ovarian carcinoma (HGSOC) tissues, and high HMGB3 levels indicated shorter overall survival and drug resistance in HGSOC. The overexpression of HMGB3 increased the insensitivity of ovarian cancer to PARPi, whereas HMGB3 knockdown reduced PARPi resistance. Mechanistically, PARP1 was identified as a novel interaction partner of HMGB3, which could be blocked using olaparib and was enhanced upon DNA damage conditions. We further showed that loss of HMGB3 induced PARP1 trapping at DNA lesions and inhibited the PARylation activity of PARP1, resulting in an increased DNA damage response and cell apoptosis. The PARPi-resistant role of HMGB3 was also verified in a xenograft mouse model. In conclusion, HMGB3 promoted PARPi resistance via interacting with PARP1, and the targeted inhibition of HMGB3 might overcome PARPi resistance in ovarian cancer therapy.

Orexin neurons play an important role in stress-related mental disorders including post-traumatic stress disorder (PTSD). Anxiety- and depression-related symptoms commonly occur in combination with PTSD. However, the role of the orexin system in mediating alterations in these affective symptoms remains unclear. The medial prefrontal cortex (mPFC) is implicated in both cognitive and emotional processing. In the present study, we investigated anxiety- and depression-related behavioral changes using the elevated plus maze, the sucrose preference test, and the open field test in male rats with single prolonged stress (SPS) induced-PTSD. The expression of orexin-A in the hypothalamus and orexin receptors (OX1R and OX2R) in the mPFC was detected and quantified by immunohistochemistry, western blotting, and real-time polymerase chain reaction. We found that the SPS rats exhibited enhanced levels of anxiety, reduced exploratory activities, and anhedonia. Furthermore, SPS resulted in reductions in the expression of orexin-A in the hypothalamus and the increased the expression of OX1R in the mPFC. The intracerebroventricular administration of orexin-A alleviated behavioral changes in SPS rats and partly restored the increased levels of OX1R in the mPFC. These results suggest that the orexin system plays a role in the anxiety- and depression-related symptoms observed in PTSD.

Objective To improve the understanding and the diagnosis of intracranial ependymal tumors. Methods The clinical, radiological and prognostic features of 48 supratentorial extraventricular ependymomas and 74 intraventricular ependymomas were summarized and compared. Results Supratentorial extraventricular ependymomas, most often located in the frontal lobe (33.3%) and classified as grade III (75.0%), had relatively large eccentric cysts (3.07 ± 2.03 cm), significant enhancement (84.8%), low apparent diffusion coefficient (ADC) values, and associated with higher mortality (41.3%). The majority of intraventricular lesions occurred in the fourth ventricle (86.5%) and classified as grade II (78.4%), had relatively small and multiple cystic changes (1.04 ± 0.87 cm), slight or moderate enhancement (76.9%), high ADC values and associated with lower mortality (20.7%). There were few significant differences between grade II and grade III tumors in these 2 groups, respectively. Young age, high grade and low ADC values are worse prognostic indicators for patients with supratentorial extraventricular ependymomas, but not for those with intraventricular ependymomas. Conclusions Conventional radiological features, combined with clinical manifestations and quantitative information provided by diffusion-weighted imaging, may not only enhance the diagnosis and assist in determining prognosis but also provide a better pathophysiological understanding of intracranial ependymal tumors.

Behavioral and neuroimaging studies have implicated the hippocampus as a cardinal neural structure in major depressive disorder (MDD) pathogenesis. The hippocampal subregion-specific structural and functional abnormalities in MDD remain unknown.Multimodal magnetic resonance imaging (MRI) was acquired in 140 patients with MDD and 44 age- and sex-matched healthy controls (HCs). We quantified hippocampal subregional volumes and fractional anisotropy (FA) following a structural and diffusion MRI data analysis processing stream. Hippocampal subregional networks were established using seed-based functional connectivity (FC) analysis. Univariate analysis was used to investigate the differences between the two groups. Significant subfield metrics were correlated with depression severity.Compared with HCs, we did not find significant differences in subregional volumes or FA metrics in the MDD group. The MDD group exhibited a significantly weaker connectivity of the right hippocampal subregional networks with the temporal cortex (extending to the insula) and basal ganglia but showed increased connectivity of the right subiculum to the bilateral lingual gyrus. The FC between the right cornu ammonis 1 and right fusiform, between the right hippocampal amygdala transition area and the bilateral basal ganglia, were negatively correlated with depression severity (r = -0.224, p = 0.010; r = -0.196, p = 0.025, respectively) in the MDD group.This study did not consider the longitudinal changes in the structure and functional connectivity of the hippocampal subregion.These findings advance our understanding of the neurobiological basis of depression by identifying the hippocampal subregional structural and functional abnormalities.

Medial prefrontal cortex (MPFC) and other regions like the occipital cortex (OC) exhibit abnormal neural activity in major depressive disorder (MDD). Their relationship to specific biochemical, psychophysical, and psychopathological changes remains unclear, though. For that purpose, we focus on a particular subregion in OC, namely middle temporal (MT) visual area that is known to mediate the perception of visual motion. Using high-field 7 T magnetic resonance imaging (MRI), including resting state functional MRI and proton magnetic resonance spectroscopy, the amplitude of low-frequency fluctuations (ALFF) of the blood oxygen level-dependent signal in MT, MT-seeded functional connectivity (FC), and gamma-aminobutyric acid (GABA) in MT were investigated. Applying the vision motion psychophysical task, the motion suppression index of subjects was also examined. We demonstrate significantly elevated neural variability (as measured by ALFF) in MT together with decreases in both MT GABA and motion suppression in our MDD sample. Unlike in healthy subjects, MT neural variability no longer modulates the relationship of MT GABA and motion suppression in MDD. MT also exhibits reduction in global inter-regional FC to MPFC in MDD. Finally, elevated MT ALFF relates to specifically retardation in behavior as measured by the Hamilton subscore. Together, MT provides a strong candidate for biomarker in MDD.

Supplemental Digital Content is available in the text, Background: Recent genome-wide association studies have identified an important role of T-cell receptor α (TRA) gene in the development of narcolepsy type 1. However, the role of TRA haplotype polymorphisms in the symptomatic diversity of narcolepsy remains unclear. This study aimed to investigate whether TRA polymorphisms can influence the symptomatic diversity of narcolepsy. Methods: Totally, 903 patients with narcolepsy type 1 were included in the study. Patients were divided into different groups according to their symptoms. First, 13 genotyped single nucleotide polymorphisms in the TRA were assessed for their association with symptoms of narcolepsy. We used the Chi-square test to determine differences in genotype frequencies in patients with narcolepsy. Further, we identified the haplotypes and variations of the TRA and tested their association with the symptoms of narcolepsy using a logistic regression model. Results: According to the results of the logistic regression, TRA haplotypes TG and CT were significantly associated with auditory hallucination, with odds ratios of 1.235 (95% confidence interval [CI], 1.012–1.507) and 1.236 (95% CI, 1.012–1.511), respectively (P