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Abstract The concept of a healthy lifestyle is receiving increasing attention. This study sought to identify an optimal healthy lifestyle profile associated with sleep health in general population of China. An online cross-sectional survey was conducted from June to July 2022. Six healthy lifestyle factors were assessed: healthy diet, regular physical exercise, never smoking, never drinking alcohol, low sedentary behavior, and normal weight. Participants were categorized into the healthy lifestyle (5-6 factors), average (3-4 factors), and unhealthy lifestyle groups (0-2 factors). The study’s primary outcome was sleep health, which included sleep quality, duration, pattern, and the presence of any sleep disorder or disturbance, including insomnia, excessive daytime sleepiness, obstructive apnea syndrome, and narcolepsy. Multivariable logistic regression analysis was applied to explore lifestyles associated with the selected sleep health outcomes. 41,061 individuals were included, forming 18.8% healthy, 63.8% average, and 17.4% unhealthy lifestyle groups. After adjusting for covariates, participants with healthy lifestyle were associated with a higher likelihood of good sleep quality (OR = 1.56, 95% CI = 1.46–1.68), normal sleep duration (OR = 1.60, 95% CI = 1.49–1.72), healthy sleep pattern (OR = 2.15, 95% CI = 2.00–2.31), and lower risks of insomnia (OR = 0.66, 95% CI = 0.61–0.71), excessive daytime sleepiness (OR = 0.66, 95% CI = 0.60–0.73), and obstructive apnea syndrome (OR = 0.40, 95% CI = 0.37–0.43), but not narcolepsy (OR = 0.92, 95% CI = 0.83–1.03), compared to those with unhealthy lifestyle. This large cross-sectional study is the first to our knowledge to quantify the associations of a healthy lifestyle with specific aspects of sleep health. The findings offer support for efforts to improve sleep health by modulating lifestyle.

Abstract The proto-oncogene MYC encodes a nuclear transcription factor that has an important role in a variety of cellular processes, such as cell cycle progression, proliferation, metabolism, adhesion, apoptosis, and therapeutic resistance. MYC amplification is consistently observed in aggressive forms of several solid malignancies and correlates with poor prognosis and distant metastases. While the tumorigenic effects of MYC in patients with head and neck squamous cell carcinoma (HNSCC) are well known, the molecular mechanisms by which the amplification of this gene may confer treatment resistance, especially to immune checkpoint inhibitors, remains under-investigated. Here we present a unique case of a patient with recurrent/metastatic (R/M) HNSCC who, despite initial response to nivolumab-based treatment, developed rapidly progressive metastatic disease after the acquisition of MYC amplification. We conducted comparative transcriptomic analysis of this patient’s tumor at baseline and upon progression to interrogate potential molecular processes through which MYC may confer resistance to immunotherapy and/or chemoradiation and used TCGA-HNSC dataset and an institutional cohort to further explore clinicopathologic features and key molecular networks associated with MYC amplification in HNSCC. This study highlights MYC amplification as a potential mechanism of immune checkpoint inhibitor resistance and suggest its use as a predictive biomarker and potential therapeutic target in R/M HNSCC.

Abstract Background Endotracheal intubation is challenging during cardiopulmonary resuscitation, and video laryngoscopy has showed benefits for this procedure. The aim of this study was to compare the effectiveness of various intubation approaches, including the bougie first, preloaded bougie, endotracheal tube (ETT) with stylet, and ETT without stylet, on first-attempt success using video laryngoscopy during chest compression. Methods This was a randomized crossover trial conducted in a general tertiary teaching hospital. We included anesthesia residents in postgraduate year one to three who passed the screening test. Each resident performed intubation with video laryngoscopy using the four approaches in a randomized sequence on an adult manikin during continuous chest compression. The primary outcome was the first-attempt success defined as starting ventilation within a one minute. Results A total of 260 endotracheal intubations conducted by 65 residents were randomized and analyzed with 65 procedures in each group. First-attempt success occurred in 64 (98.5%), 57 (87.7%), 56 (86.2%), and 46 (70.8%) intubations in the bougie-first, preloaded bougie, ETT with stylet, and ETT without stylet approaches, respectively. The bougie-first approach had a significantly higher possibility of first-attempt success than the preloaded bougie approach [risk ratio (RR) 8.00, 95% confidence interval (CI) 1.03 to 62.16, P = 0.047], the ETT with stylet approach (RR 9.00, 95% CI 1.17 to 69.02, P = 0.035), and the ETT without stylet approach (RR 19.00, 95% CI 2.62 to 137.79, P = 0.004) in the generalized estimating equation logistic model accounting for clustering of intubations operated by the same resident. In addition, the bougie first approach did not result in prolonged intubation or increased self-reported difficulty among the study participants. Conclusions The bougie first approach with video laryngoscopy had the highest possibility of first-attempt success during chest compression. These results helped inform the intubation approach during CPR. However, further studies in an actual clinical environment are warranted to validate these findings. Trial registration Clinicaltrials.gov; identifier: NCT05689125; date: January 18, 2023.

Abstract Genetically lean and obese individuals have distinct intestinal microbiota and function. However, the underlying mechanisms of the microbiome heterogeneity and its regulation on epithelial function such as intestinal stem cell (ISC) fate remain unclear. Employing pigs of genetically distinct breeds (obese Meishan and lean Yorkshire), this study reveals transcriptome‐wide variations in microbial ecology of the jejunum, characterized by enrichment of active Lactobacillus species, notably the predominant Lactobacillus amylovorus (L. amylovorus), and lactate metabolism network in obese breeds. The L. amylovorus‐dominant heterogeneity is paralleled with epithelial functionality difference as reflected by highly expressed GPR81, more proliferative ISCs and activated Wnt/β‐catenin signaling. Experiments using in‐house developed porcine jejunal organoids prove that live L. amylovorus and its metabolite lactate promote intestinal organoid growth. Mechanistically, L. amylovorus and lactate activate Wnt/β‐catenin signaling in a GPR81‐dependent manner to promote ISC‐mediated epithelial proliferation. However, heat‐killed L. amylovorus fail to cause these changes. These findings uncover a previously underrepresented role of L. amylovorus in regulating jejunal stem cells via Lactobacillus‐lactate‐GPR81 axis, a key mechanism bridging breed‐driven intestinal microbiome heterogeneity with ISC fate. Thus, results from this study provide new insights into the role of gut microbiome and stem cell interactions in maintaining intestinal homeostasis.

ObjectiveThis study aimed to investigate the regulatory role of astrocyte-derived exosomes and their microRNAs (miRNAs) in modulating neuronal pyroptosis during cerebral ischemia.MethodsAstrocyte-derived exosomes were studied for treating cerebral ischemia in both in vitro and in vivo models. The effects of astrocyte-derived exosomes on neuroinflammation were investigated by analyzing exosome uptake, nerve damage, and pyroptosis protein expression. High throughput sequencing was used to identify astrocyte-derived exosomal miRNAs linked to pyroptosis, followed by validation via qRT‒PCR. The relationship between these miRNAs and NLRP3 was studied using a dual luciferase reporter assay. This study used miR-378a-5p overexpression and knockdown to manipulate OGD injury in nerve cells. The impact of astrocyte-derived exosomal miR-378a-5p on the regulation of cerebral ischemic neuroinflammation was assessed through analysis of nerve injury and pyroptosis protein expression.ResultsOur findings demonstrated that astrocyte-derived exosomes were internalized by neurons both in vitro and in vivo. Additionally, Astrocyte-derived exosomes displayed a neuroprotective effect against OGD-induced neuronal injury and brain injury in the ischemic cortical region of middle cerebral artery occlusion (MCAO) rats while also reducing pyroptosis. Further investigations revealed the involvement of astrocyte-derived exosomal miR-378a-5p in regulating pyroptosis by inhibiting NLRP3. The overexpression of miR-378a-5p mitigated neuronal damage, whereas the knockdown of miR-378a-5p increased NLRP3 expression and exacerbated pyroptosis, thus reversing this neuroprotective effect.ConclusionAstrocyte-derived exosomal miR-378a-5p has a neuroprotective effect on cerebral ischemia by suppressing neuroinflammation associated with NLRP3-mediated pyroptosis.Further research is required to comprehensively elucidate the signaling pathways by which astrocyte-derived exosomal miR-378a-5p modulates neuronal pyroptosis.

The electron-phonon (el-ph) and phonon-phonon interactions play a key role in determining electronic and thermal transport properties, respectively, in promising two-dimensional (2D) semiconductor devices. In this study, we investigated el-ph interactions using Wannier-Fourier interpolation method and renormalized phonon scattering considering finite-temperature effects in Bi2TeSe2 monolayer. The results show that the optical phonon modes dominate the carrier scattering, where level repulsion induced by crystal field splitting and spin-orbit coupling (SOC) effect effectively suppresses intervalley scattering, leading to high hole mobility. Moreover, the strong anharmonicity in Bi2TeSe2 monolayer results in the temperature-dependent softening of its optical phonons, along with a corresponding variation in interatomic force constants (IFCs). As a result, the lattice thermal conductivity is remarkably low and exhibits weak temperature dependence. Finally, the predicted dimensionless thermoelectric figure of merit exceeds unity in the range of 200–800 K, indicating the potential of Bi2TeSe2 monolayer for thermoelectric applications. This work provides new insights into the elimination of intervalley scattering by crystal field splitting and SOC effects, and paves the way for the evaluation of thermoelectric properties of materials with complex scattering mechanisms and strong anharmonicity.

This paper presents an experimental study on the compressive properties and creep behavior of Mg-Gd-Y-Zn-Mn-Nd alloy. A total of 42 specimens are prepared and tested, including 18 compression tests and 24 creep tests. The investigation aims to evaluate the influence of material orientation, temperature, and initial stress (for creep test only) on the compressive behavior of the Mg-Gd-Y-Zn-Mn-Nd alloy. First, the results of compression tests are analyzed, revealing insights into the anisotropic behavior, failure mode, yield strength, ultimate compressive strength, and failure strain of the Mg-Gd-Y-Zn-Mn-Nd alloy under compressive loading. Then, according to the experimental data from creep tests, where the steady creep rate, stress exponent and activation energy are calibrated. Furthermore, the creep mechanisms of the Mg-Gd-Y-Zn-Mn-Nd alloy under various material orientations are discussed. Additionally, the authors analyze and compare the Electron Backscatter Diffraction (EBSD) data of the Mg-Gd-Y-Zn-Mn-Nd alloy before and after undergoing compressive creep. Finally, based on the test results, a mathematical model is proposed to describe the development of compressive creep strain.

ABSTRACTIntestinal stem cells (ISCs) play a pivotal role in gut physiology by governing intestinal epithelium renewal through the precise regulation of proliferation and differentiation. The gut microbiota interacts closely with the epithelium through myriad of actions, including immune and metabolic interactions, which translate into tight connections between microbial activity and ISC function. Given the diverse functions of the gut microbiota in affecting the metabolism of macronutrients and micronutrients, dietary nutrients exert pronounced effects on host-microbiota interactions and, consequently, the ISC fate. Therefore, understanding the intricate host-microbiota interaction in regulating ISC homeostasis is imperative for improving gut health. Here, we review recent advances in understanding host-microbiota immune and metabolic interactions that shape ISC function, such as the role of pattern-recognition receptors and microbial metabolites, including lactate and indole metabolites. Additionally, the diverse regulatory effects of the microbiota on dietary nutrients, including proteins, carbohydrates, vitamins, and minerals (e.g. iron and zinc), are thoroughly explored in relation to their impact on ISCs. Thus, we highlight the multifaceted mechanisms governing host–microbiota interactions in ISC homeostasis. Insights gained from this review provide strategies for the development of dietary or microbiota-based interventions to foster gut health.

Basic leucine zipper (bZIP) transcription factors (TFs) regulate plant development, growth, and secondary metabolism. The formation of red bark of new ornamental cultivar 'Gantong 1' is regulated mainly by anthocyanin anabolism. However, it is unclear whether and which bZIP TFs are involved in this process. We identified 89 genes encoding CcbZIP TFs in Cinnamomum camphora genome that could be divided into 14 subfamilies with similar gene structures and conserved motifs. CcbZIP38 and CcbZIP57 were highly conserved compared to HY5 in Arabidopsis thaliana and they were highly expressed in the bark and leaves of 'Gantong 1' at different stages. The target gene enrichment analysis showed that indicating indirect involvement of CcbZIP38 and CcbZIP57 in the regulation of anthocyanin synthesis. Our study contributes to understanding the molecular mechanism of anthocyanin synthesis regulation by CcbZIP TFs and provides a theoretical basis for genetic improvement of ornamental traits in C. camphora.

Summary: Background: A variety of symptoms, particularly cognitive, psychiatric and neurological symptoms, may persist for a long time among individuals recovering from COVID-19. However, the underlying mechanism of these brain abnormalities remains unclear. This study aimed to investigate the long-term neuroimaging effects of COVID-19 infection on brain functional activities using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Fifty-two survivors 27 months after infection (mild-moderate group: 25 participants, severe-critical: 27 participants), from our previous community participants, along with 35 healthy controls, were recruited to undergo fMRI scans and comprehensive cognitive function measurements. Participants were evaluated by subjective assessment of Cognitive Failures Questionnaire-14 (CFQ-14) and Fatigue Scale-14 (FS-14), and objective assessment of Montreal Cognitive Assessment (MoCA), N-back, and Simple Reaction Time (SRT). Each had rs-fMRI at 3T. Measures such as the amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were calculated. Findings: Compared with healthy controls, survivors of mild-moderate acute symptoms group and severe-critical group had a significantly higher score of cognitive complains involving cognitive failure and mental fatigue. However, there was no difference of cognitive complaints between two groups of COVID-19 survivors. The performance of three groups was similar on the score of MoCA, N-back and SRT. The rs-fMRI results showed that COVID-19 survivors exhibited significantly increased ALFF values in the left putamen (PUT.L), right inferior temporal gyrus (ITG.R) and right pallidum (PAL.R), while decreased ALFF values were observed in the right superior parietal gyrus (SPG.R) and left superior temporal gyrus (STG.L). Additionally, decreased ReHo values in the right precentral gyrus (PreCG.R), left postcentral gyrus (PoCG.L), left calcarine fissure and surrounding cortex (CAL.L) and left superior temporal gyrus (STG.L). Furthermore, significant negative correlations between the ReHo values in the STG.L, and CFQ-14 and mental fatigue were found. Interpretation: This long-term study suggests that individuals recovering from COVID-19 continue to experience cognitive complaints, psychiatric and neurological symptoms, and brain functional alteration. The rs-fMRI results indicated that the changes in brain function in regions such as the putamen, temporal lobe, and superior parietal gyrus may contribute to cognitive complaints in individuals with long COVID even after 2-year infection. Funding: The National Programs for Brain Science and Brain-like Intelligence Technology of China, the National Natural Science Foundation of China, Natural Science Foundation of Beijing Municipality of China, and the National Key Research and Development Program of China.

Abstract The 2D semiconductors are an ideal platform for exploration of bosonic fluids composed of coupled photons and collective excitations of atoms or excitons, primarily due to large excitonic binding energies and strong light‐matter interaction. Based on first‐principles calculations, it is demonstrated that the phonon polaritons formed by two infrared‐active phonon modes in monolayer MoSi2N4 and WSi2N4 possess ultra‐high confinement factors of around ≈105 and 103, surpassing those of conventional polaritonic thin‐film materials by two orders of magnitude. It is observed that the first bright exciton possesses a substantial binding energies of 750 and 740 meV in these two monolayers, with the radiative recombination lifetimes as long as 25 and 188 ns, and the Rabi splitting of the formed cavity‐exciton polaritons reaching 373 and 321 meV, respectively. The effective masses of the cavity exciton polaritons are approximately 10−5me, providing the potential for high‐temperature quantum condensation. The ultra‐confined and ultra‐low‐loss phonon polaritons, as well as strongly‐coupled cavity exciton polaritons with ultra‐small polaritonic effective masses in these two monolayers, offering the flexible control of light at the nanoscale, probably leading to practical applications in nanophotonics, meta‐optics, and quantum materials.

An increasing amount of research has shown that glycosylation plays a crucial role in autoimmune diseases (ADs), prompting our interest in conducting research on the knowledge framework and hot topics in this field based on bibliometric analysis. Studies on glycosylation in the field of ADs from 2003 to 2023 were collected by searching the Web of Science Core Collection database. Bibliometric analysis was conducted using VOSviewer, CiteSpace, and Bibliometrix software. This study included a total of 530 studies. According to the H, G, and M indices, the United States has made the most contributions worldwide, with China making significant contributions in recent years. Leiden University from the Netherlands ranks among the top institutions in terms of publication and citation rankings, with the institution's author Manfred Wuhrer contributing the most to this field. Frontiers in Immunology is the journal with the highest H-index. Research in this field has focused on antibody glycosylation, particularly the specific glycosylation of IgG and IgA, and its role in various ADs. The application of glycoengineering glycosylated proteins in the synthesis of targeted monoclonal antibodies, drug delivery, and regenerative medical materials may be a new trend in the treatment of ADs. Artificial intelligence is an emerging tool in glycobiology. This study summarizes the objective data on glycosylation in the field of AD publications in recent years, providing a reference for researchers in this field.

Abstract The electron-phonon (el-ph) and phonon-phonon interactions play crucial roles in determining the electronic and thermal transport properties of materials. Using the group theory and ab-initio calculations, we have derived the full-landscape selection rules for intravalley and intervalley scattering for carriers in 2D silicon and germanium allotropes with low buckled (LB) and large honeycomb dumbbell (LHD) structures, showing dominant role of optical modes in total el-ph coupling in LHD Si/Ge due to most el-ph scattering channels via acoustic modes blocked by symmetries. Remarkably, we show that due to the relatively large optical phonon bandwidth and “bunching effect" of acoustic phonon bands, the selection rules of three-phonon interactions reveal the dominant ooo and aoo channels in LHD and LB Si/Ge, respectively, and the temprature-induced effects significantly increase the ratio between mode-resolved four-phonon interactions and three-phonon interactions in most of the phonon-frequency region, finally leading to the low thermal conductivities in both LB and LHD Si/Ge. Furthermore, we observe the anomalous temperature-dependent thermal conductivities in LHD Ge, resulted from the vanishing quasi-acoustic-optical phonon gap under the temperature-induced effects. By considering full el-ph coupling and higher-order anharmonic phonon-phonon interactions, the maximal thermoelectric figures of merits in LHD Si and LB Ge are found to reach 1.06 and 0.66 at 700 K, respectively, significantly surpassing their bulk counterparts. Our work is poised to stimulate wide-ranging exploration into phonon transport across diverse materials, and benefits both fundamental knowledge and advanced technologies of 2D Si/Ge allotropes.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nasal cavity and paranasal sinuses. The role of neutrophils in the pathogenesis of CRSwNP has attracted more attention in recent years, due to its association with more severe disease and reduced steroid responsiveness. Lipocalin-2 (LCN2) has been found to modulate neutrophils infiltration in other neutrophilic inflammation including inflammatory bowel disease, rheumatoid arthritis, and psoriasis. The aim was to evaluate the expression and regulator role of LCN2 in neutrophilic inflammation in CRSwNP, and its role as a potential biomarker predicting non-eosinophilic CRSwNP (neCRSwNP). Methods: Bioinformatic analysis, immunostainings, real-time PCR and ELISA were used to analyze the expression and location of LCN2 in nasal tissues. The expression of proinflammatory mediators were assessed in nasal tissues and secretions. LCN2 production in human nasal epithelial cells (HNECs) and neutrophils, as well as its role in neutrophilic inflammation was evaluated by in vitro experiments. Results: LCN2 was mainly located in neutrophils and HNECs of nasal polyps. LCN2 expression was also significantly higher in the polyp tissue and nasal secretions from patients with neCRSwNP. The LCN2 levels were positively correlated with type 3 inflammation markers, including G-CSF, IL-8, and IL-17. LCN2 expression could be upregulated by IL-17 A and TNF-α in HNECs, and LCN2 could also promote the expression of IL-8 in dispersed polyp cells and HNECs. Conclusions: LCN2 could serve as a novel biomarker predicting patients with neCRSwNP, and the increased expression of LCN2 may participate in the pathogenesis of neCRSwNP.

Pancreatic cancer-related pain (PCRP) gains widespread attention for its high prevalence, extreme complexity, poor prognosis, and decreased survival rate. Current treatment of PCRP remains unsatisfactory since the underlying mechanism is not clear. The occurrence of PCRP is mainly related to the neurotropic nature of pancreatic cancer, and perineural invasion, neural remodeling and plasticity play important roles. Upon the understanding of PCRP mechanism, the management of PCRP is a multidisciplinary and multifaceted strategy. Traditional pain medications, invasive or intervention treatment, psychological support, integrative therapy, and palliative care are all the potential aspects for the management of PCRP.

Bovine viral diarrhea virus (BVDV) is an RNA virus associated with severe economic losses in animal production. Effective vaccination and viral surveillance are urgent for the prevention and control of BVDV infection. However, the application of traditional modified live vaccines and inactivated vaccines is faced with tremendous challenges. In the present study, we describe the preclinical efficacy of two BVDV mRNA vaccines tested in mice and guinea pigs, followed by a field trial in goats, where they were compared to a commercial vaccine (formaldehyde inactivated). The two mRNAs were engineered to express the envelope protein E2 of BVDV-1, the most prevalent subtype across the world, through a 5′ cap-dependent or independent fashion. Better titers of neutralizing antibodies against BVDV-1 were achieved using the capped RNA in the sera of mice and guinea pigs, with maximum values reaching 9.4 and 13.7 (by −log2), respectively, on the 35th day post-vaccination. At the same time point, the antibody levels in goats were 9.1 and 10.2 for the capped and capless RNAs, respectively, and there were no significant differences compared to the commercial vaccine. The animals remained healthy throughout the experiment, as reflected by their normal leukogram profiles. Collectively, our findings demonstrate that mRNA vaccines have good safety and immunogenicity, and we laid a strong foundation for the further exploitation of efficient and safe BVDV vaccines.

Abstract Crystalline frameworks containing incorporated flexible macrocycle units can afford new opportunities in molecular recognition and selective separation. However, such functionalized frameworks are difficult to prepare and challenging to characterize due to the flexible nature of macrocycles, which limits the development of macrocycle-based crystalline frameworks. Herein, we report the design and synthesis of a set of metal–organic frameworks (MOFs) containing pillar[5]arene units. The pillar[5]arene units were uniformly embedded in the periodic frameworks. Single crystal X-ray diffraction analysis revealed an interpenetrated network that appears to hinder the rotation of the pillar[5]arene repeating units in the frameworks, and it therefore resulted in the successful determination of the precise pillar[5]arene host structure in a MOF crystal. These MOFs can recognize paraquat and 1,2,4,5-tetracyanobenzene in solution and selectively remove trace pyridine from toluene with relative ease. The work presented here represents a critical step towards the synthesis of macrocycle-incorporated crystalline frameworks with well-defined structures and functional utility.

Abstract Background We aimed to investigate the effects of intermittent bolus paravertebral block on analgesia and recovery in open hepatectomy. Methods Eighty 18–70 years old, American Society of Anesthesiologists level I-III patients scheduled for hepatectomy with a J-shaped subcostal incision were enrolled and randomized to receive either intermittent bolus paravertebral ropivacaine (0.5% loading, 0.2% infusion) or 0.9% saline infusion at 1:1 ratio (25 ml loading before surgery, 0.125 ml/kg/h bolus for postoperative 48 h). The primary outcome was set as postoperative 48 h cumulative intravenous morphine consumption recorded by a patient-controlled analgesic pump. Results Thirty-eight patients in each group completed the study. The cumulative morphine consumptions were lower in the paravertebral block than control group at postoperative 24 (difference -10.5 mg, 95%CI -16 mg to -6 mg, P

Segmenting the left ventricle from the transgastric short-axis views (TSVs) on transesophageal echocardiography (TEE) is the cornerstone for cardiovascular assessment during perioperative management. Even for seasoned professionals, the procedure remains time-consuming and experience-dependent. The current study aims to evaluate the feasibility of deep learning for automatic segmentation by assessing the validity of different U-Net algorithms. A large dataset containing 1388 TSV acquisitions was retrospectively collected from 451 patients (32% women, average age 53.42 years) who underwent perioperative TEE between July 2015 and October 2023. With image preprocessing and data augmentation, 3336 images were included in the training set, 138 images in the validation set, and 138 images in the test set. Four deep neural networks (U-Net, Attention U-Net, UNet++, and UNeXt) were employed for left ventricle segmentation and compared in terms of the Jaccard similarity coefficient (JSC) and Dice similarity coefficient (DSC) on the test set, as well as the number of network parameters, training time, and inference time. The Attention U-Net and U-Net++ models performed better in terms of JSC (the highest average JSC: 86.02%) and DSC (the highest average DSC: 92.00%), the UNeXt model had the smallest network parameters (1.47 million), and the U-Net model had the least training time (6428.65 s) and inference time for a single image (101.75 ms). The Attention U-Net model outperformed the other three models in challenging cases, including the impaired boundary of left ventricle and the artifact of the papillary muscle. This pioneering exploration demonstrated the feasibility of deep learning for the segmentation of the left ventricle from TSV on TEE, which will facilitate an accelerated and objective alternative of cardiovascular assessment for perioperative management.

Sleep deprivation (SD) triggers mitochondrial dysfunction and neural inflammation, leading to cognitive impairment and mental issues. However, the mechanism involving mitochondrial dysfunction and neural inflammation still remains unclear. Here, we report that SD rats exhibited multiple behavioral disorders, brain oxidative stress, and robust brain mitochondrial DNA (mtDNA) oxidation. In particular, SD activated microglia and microglial mtDNA efflux to the cytosol and provoked brain pro-inflammatory cytokines. We observed that the mtDNA efflux and pro-inflammatory cytokines significantly reduced with the suppression of the mtDNA oxidation. With the treatment of a novel mitochondrial nutrient, hydroxytyrosol butyrate (HTHB), the SD-induced behavioral disorders were significantly ameliorated while mtDNA oxidation, mtDNA release, and NF-κB activation were remarkably alleviated in both the rat brain and the N9 microglial cell line. Together, these results indicate that microglial mtDNA oxidation and the resultant release induced by SD mediate neural inflammation and HTHB prevents mtDNA oxidation and efflux, providing a potential treatment for SD-induced mental issues.

Abstract Spinal ultrasonography has increasingly been used to image axial structures from the cervical to sacral region in recent years. In this work, we propose a comprehensive, systematic cervical scanning protocol that we refined as a route map, especially for beginners, to facilitate teaching, learning, diagnosis, and treatment in clinical pain practice. As a simple and clear tool to demonstrate the scanning protocol, the route map is delineated with rectangles, lines, and arrows. The rectangles represent the positions of the transducer, the arrows indicate route directions, and the lines show the routes of transducer movement. In this article, we describe cervical spinal ultrasonography to illustrate the route map interpretation, scanning protocol and target anatomical structures in detail. We believe that this comprehensive, clear, systematic, and portable route map will be beneficial for inexperienced pain clinicians and ultrasound beginners.

Abstract Objectives Previous studies have shown that there may be a positive correlation between serum uric acid levels and hyperthyroidism. However, the relationship between thyroid function and serum uric acid in healthy people is unclear. This study analyzed the relationship between impaired thyroid hormone sensitivity and serum uric acid levels, and presented them in quantitative form. Research design and methods This is a cross-sectional study of 4460 adults (male: 2300; female: 2160) who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2010. Parameters representing central sensitivity to thyroid hormones were calculated as: thyroid feedback quantile-based index (TFQIFT4), thyroid stimulating hormone index (TSHI), and total thyroxine (T4) resistance index (TT4RI); Peripheral sensitivity to thyroid hormone was evaluated by FT3/FT4 ratio. In addition, we have innovated total triiodothyronine (T3) resistance index (TT3RI) and TFQIFT3 indexes based on FT3 and TSH. Multiple linear regression models were used to evaluate the correlation between thyroid resistance index and serum uric acid, and the results were presented graphically as smooth curve fittings. Results Higher levels of serum uric acid were associated with decreased sensitivity to thyroid hormones in euthyroid individuals. In conjunction with an increase in the thyroid hormone sensitivity index value, uric acid levels gradually increased as well. Furthermore, we found a segmented relationship between TT3RI and serum uric acid changes. The saturation and threshold analyses indicated that 18.85 was the turning point (logarithmic likelihood ratio test = 0.036). When TT3RI 18.85, there was a significant rise in serum uric acid with an increase in TT3RI [β(95% CI) 3.94 (0.94, 6.95), P = 0.010]. A further finding of the interaction test was that impaired thyroid hormone sensitivity and uric acid changes vary among different age groups and BMI levels. Conclusions Decreased sensitivity to thyroid hormones was associated with high levels of serum uric acid in people with normal thyroid function. The interaction test shows that different age groups and BMI groups impact the association between impaired thyroid hormone sensitivity and serum uric acid. Furthermore, smooth curve fitting revealed a segmental relationship between TT3RI and serum uric acid levels.

Abstract Background With the rise of reported mental disorders and behavioral issues after the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, psychiatrists and mental health care are urgently needed more than ever before. The psychiatric career carries a high emotional burden and stressful demands, which bring issues on psychiatrists’ mental health and well-being into question. To investigate the prevalence and risk factors of depression, anxiety, and work burnout among psychiatrists in Beijing during the COVID-19 pandemic. Methods This cross-sectional survey was conducted from January 6 to January 30, 2022, two years after COVID-19 was declared a global pandemic. Recruitment was performed using a convenience sample approach by sending online questionnaires to psychiatrists in Beijing. The symptoms of depression, anxiety, and burnout were evaluated using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Maslach Burnout Inventory-General Survey (MBI-GS). The perceived stress and social support were measured by the Chinese Perceived Stress Scale (CPSS) and Social Support Rating Scale (SSRS), respectively. Results The data of 564 psychiatrists (median [interquartile range] age, 37 [30–43] years old) of all 1532 in Beijing were included in the statistical analysis. The prevalence of symptoms of depression, anxiety and burnout were 33.2% (95% CI, 29.3-37.1%, PHQ-9 ≥ 5), 25.4% (95% CI, 21.8-29.0%, GAD-7 ≥ 5) and 40.6% (95% CI, 36.5-44.7%, MBI-GS ≥ 3 in each of the three subdimensions), respectively. The psychiatrist with a higher score on perceived stress was more likely to suffer from depressive symptoms (adjusted odds ratios [ORs]: 4.431 [95%CI, 2.907–6.752]); the anxiety symptoms (adjusted ORs: 8.280 [95%CI, 5.255–13.049]), and the burnout conditions (adjusted ORs: 9.102 [95%CI, 5.795–14.298]). Receiving high social support was an independent protective factor against symptoms of depression (adjusted ORs: 0.176 [95%CI, [0.080–0.386]), anxiety (adjusted ORs: 0.265 [95%CI, 0.111–0.630]) and burnout (adjusted ORs: 0.319 [95%CI, 0.148–0.686]). Conclusions Our data suggest a considerable proportion of psychiatrists also suffer from depression, anxiety, and burnout. Perceived stress and social support influence depression, anxiety, and burnout. For public health, we must work together to reduce the pressure and increase social support to mitigate mental health risks in psychiatrists.

Ovarian cancer (OC) is one of the most lethal malignancies of the female reproductive system. OC patients are usually diagnosed at advanced stages due to the lack of early diagnosis. The standard treatment for OC includes a combination of debulking surgery and platinum-taxane chemotherapy, while several targeted therapies have recently been approved for maintenance treatment. The vast majority of OC patients relapse with chemoresistant tumors after an initial response. Thus, there is an unmet clinical need to develop new therapeutic agents to overcome the chemoresistance of OC. The anti-parasite agent niclosamide (NA) has been repurposed as an anti-cancer agent and exerts potent anti-cancer activities in human cancers including OC. Here, we investigated whether NA could be repurposed as a therapeutic agent to overcome cisplatin-resistant (CR) in human OC cells. To this end, we first established two CR lines SKOV3CR and OVCAR8CR that exhibit the essential biological characteristics of cisplatin resistance in human cancer. We showed that NA inhibited cell proliferation, suppressed cell migration, and induced cell apoptosis in both CR lines at a low micromole range. Mechanistically, NA inhibited multiple cancer-related pathways including AP1, ELK/SRF, HIF1, and TCF/LEF, in SKOV3CR and OVCAR8CR cells. NA was further shown to effectively inhibit xenograft tumor growth of SKOV3CR cells. Collectively, our findings strongly suggest that NA may be repurposed as an efficacious agent to combat cisplatin resistance in chemoresistant human OC, and further clinical trials are highly warranted.

Abstract Background Ufm1-specific ligase 1 (Ufl1) and Ufm1-binding protein 1 (Ufbp1), as putative targets of ubiquitin-fold modifier 1 (Ufm1), have been implicated in several pathogenesis-related signaling pathways. However, little is known about their functional roles in liver disease. Methods Hepatocyte-specific Ufl1 Δ/Δhep and Ufbp1 Δ/Δhep mice were used to study their role in liver injury. Fatty liver disease and liver cancer were induced by high-fat diet (HFD) and diethylnitrosamine (DEN) administration, respectively. iTRAQ analysis was employed to screen for downstream targets affected by Ufbp1 deletion. Co-immunoprecipitation was used to determine the interactions between the Ufl1/Ufbp1 complex and the mTOR/GβL complex. Results Ufl1 Δ/Δhep or Ufbp1 Δ/Δhep mice exhibited hepatocyte apoptosis and mild steatosis at 2 months of age and hepatocellular ballooning, extensive fibrosis, and steatohepatitis at 6–8 months of age. More than 50% of Ufl1 Δ/Δhep and Ufbp1 Δ/Δhep mice developed spontaneous hepatocellular carcinoma (HCC) by 14 months of age. Moreover, Ufl1 Δ/Δhep and Ufbp1 Δ/Δhep mice were more susceptible to HFD-induced fatty liver and DEN-induced HCC. Mechanistically, the Ufl1/Ufbp1 complex directly interacts with the mTOR/GβL complex and attenuates mTORC1 activity. Ablation of Ufl1 or Ufbp1 in hepatocytes dissociates them from the mTOR/GβL complex and activates oncogenic mTOR signaling to drive HCC development. Conclusions These findings reveal the potential role of Ufl1 and Ufbp1 as gatekeepers to prevent liver fibrosis and subsequent steatohepatitis and HCC development by inhibiting the mTOR pathway.

Background: Millions of COVID-19 pediatric survivors are facing the risk of long COVID after recovery from acute COVID-19. The primary objective of this study was to systematically review the available literature and determine the pooled prevalence of, and risk factors for long COVID among the pediatric survivors. Methods: Studies that assessed the prevalence of, or risk factors associated with long COVID among pediatric COVID-19 survivors were systematically searched in PubMed, Embase, and Cochrane Library up to December 11th, 2022. Random effects model was performed to estimate the pooled prevalence of long COVID among pediatric COVID-19 patients. Subgroup analyses and meta-regression on the estimated prevalence of long COVID were performed by stratification with follow-up duration, mean age, sex ratio, percentage of multisystem inflammatory syndrome, hospitalization rate at baseline, and percentage of severe illness. Results: Based on 40 studies with 12,424 individuals, the pooled prevalence of any long COVID was 23.36 % ([95 % CI 15.27–32.53]). The generalized symptom (19.57 %, [95 % CI 9.85–31.52]) was reported most commonly, followed by respiratory (14.76 %, [95 % CI 7.22–24.27]), neurologic (13.51 %, [95 % CI 6.52–22.40]), and psychiatric (12.30 %, [95% CI 5.38–21.37]). Dyspnea (22.75 %, [95% CI 9.38–39.54]), fatigue (20.22 %, [95% CI 9.19–34.09]), and headache (15.88 %, [95 % CI 6.85–27.57]) were most widely reported specific symptoms. The prevalence of any symptom during 3–6, 6–12, and> 12 months were 26.41 % ([95 % CI 14.33–40.59]), 20.64 % ([95 % CI 17.06–24.46]), and 14.89 % ([95 % CI 6.09–26.51]), respectively. Individuals with aged over ten years, multisystem inflammatory syndrome, or had severe clinical symptoms exhibited higher prevalence of long COVID in multi-systems. Factors such as older age, female, poor physical or mental health, or had severe infection or more symptoms were more likely to have long COVID in pediatric survivors. Conclusions: Nearly one quarter of pediatric survivors suffered multisystem long COVID, even at 1 year after infection. Ongoing monitoring, comprehensive prevention and intervention is warranted for pediatric survivors, especially for individuals with high risk factors.

Introduction Early oral intake (EOI) is supposed to be safe and beneficial to patients’ recovery. However, the optimal timing of resuming oral intake has not been validated in thyroid and parathyroid surgery. On the other hand, a modified electromyography (EMG) endotracheal intubation protocol with real-time EMG monitoring during video laryngoscope/fibrescope-guided intubation was presented in 2022, which was regarded as an effective way to shorten the intubation time. We aimed to use Quality of Recovery-15 (QoR-15) questionnaire to compare the efficacy and safety of different EMG endotracheal intubation protocols combined with different postoperative oral intake strategy in thyroid and parathyroid surgery.Methods and analysis This prospective, single-centre, 2×2 factorial, randomised controlled trial will be conducted in the Peking Union Medical College Hospital (PUMCH), China. We plan to recruit 200 adult patients who will receive thyroid or parathyroid surgery under intraoperative nerve monitoring. Eligible patients will be randomly divided into two groups, which will receive either the modified intubation protocol (M group) or conventional intubation process (C group). After patients enter postanaesthesia care unit and Steward scores ≥4, they will be randomly divided into two groups again, which will receive early resumption of oral intake (E group) or delayed resumption of oral intake (D group). Patients will be followed up during hospitalisation and the QoR-15 questionnaire will be administered to compare the quality of recovery on the day before surgery (T0), the first day after surgery (T1) and the day of discharge (T2). The primary outcome is the QoR-15 scores at T1.Ethics and dissemination The study protocol has been approved by the Research Ethics Committee of Peking Union Medical College Hospital (IRB K-2501). All participants will give written informed consent before participation. The results from this study will be shared at conferences and disseminated in international journals.Trial registration number NCT05624463.

Background: In recent years, baroreflex activation therapy (BAT) has been utilized to treat heart failure with reduced ejection fraction (HFrEF). However, the supporting literature on its efficacy and safety is still limited. This investigation elucidates the effects of BAT in HFrEF patients to provide a reference for future clinical applications. Methods: This investigation follows Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. Relevant investigations on the use of BAT in HFrEF patients were searched and selected from 5 databases, including Web of Science, MEDLINE, PubMed, Embase, and Cochrane Library, from inception to December 2022. The methodological quality of eligible articles was assessed via the Cochrane risk of bias tool, and for meta-analysis, RevMan (5.3) was used. Results: Randomized controlled trials comprising 343 participants were selected for the meta-analysis, which revealed that in HFrEF patients, BAT enhanced the levels of LVEF (MD: 2.97, 95 % CI: 0.53 to 5.41), MLHFQ (MD: −14.81, 95 % CI: −19.57 to −10.06) and 6MWT (MD: 68.18, 95 % CI: 51.62 to 84.74), whereas reduced the levels of LVEDV (MD: −15.79, 95 % CI: −32.96 to 1.37) and DBP (MD: −2.43, 95 % CI: −4.18 to −0.68). Conclusion: It was concluded that BAT is an efficient treatment option for HFrEF patients. However, to validate this investigation, further randomized clinical trials with multiple centers and large sample sizes are needed.

To explore the correlation and causality between multidimensional sleep traits and pan-cancer incidence and mortality among patients with cancer. The multivariable Cox regression, linear and nonlinear Mendelian randomization (MR), and survival curve analyses were conducted to assess the impacts of chronotype, sleep duration, and insomnia symptoms on pan-cancer risk (N = 326,417 from United Kingdom Biobank) and mortality (N = 23,956 from United Kingdom Biobank). In the Cox regression, we observed a linear and J-shaped association of sleep duration with pan-cancer incidence and mortality among cancer patients respectively. In addition, there was a positive association of insomnia with pan-cancer incidence (HR, 1.03, 95% CI: 1.00–1.06, p = 0.035), all-cause mortality (HR, 1.17, 95% CI: 1.06–1.30, p = 0.002) and cancer mortality among cancer patients (HR, 1.25, 95% CI: 1.11–1.41, p < 0.001). In the linear MR, there was supporting evidence of positive associations between long sleep duration and pan-cancer incidence (OR, 1.41, 95% CI: 1.08–1.84, p = 0.012), and there was a positive association between long sleep duration and all-cause mortality in cancer patients (OR, 5.56, 95% CI: 3.15–9.82, p = 3.42E-09). Meanwhile, a strong association between insomnia and all-cause mortality in cancer patients (OR, 1.41, 95% CI: 1.27–1.56, p = 4.96E-11) was observed in the linear MR. These results suggest that long sleep duration and insomnia play important roles in pan-cancer risk and mortality among cancer patients. In addition to short sleep duration and insomnia, our findings highlight the effect of long sleep duration in cancer prevention and prognosis.

Background: Technetium [99Tc] methylene diphosphonate injection (99Tc-MDP) is widely used for the treatment of rheumatoid arthritis (RA), but there is still insufficient evidence for its application. Through the utilization of meta-analysis and systematic reviews, this study aimed to evaluate the effectiveness and safety of 99 TC-MDP in combination with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for RA. Methods: This study was registered on PROSPERO in advance (CRD42021220780). A systematic search was conducted in PubMed, Embase, the Cochrane Library, and multiple international public databases from their inception to April 2023 to identify clinical randomized controlled trials exploring the use of 99Tc-MDP combined with csDMARDs in the treatment of RA. Each outcome was subjected to meta-analysis, and the quality of evidence was assessed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The American College of Rheumatology's 50 %/70 % response criteria scores (ACR50/70) scores were utilized as the primary effectiveness outcomes, and risks were measured by assessing the rates of AEs. Moreover, secondary efficacy outcomes were evaluated, including the Disease Activity Score 28 (DAS28) and bone mineral density (BMD) as joint function indicators and the erythrocyte sedimentation rate (ESR) and interleukin-17 (IL-17) as inflammatory indicators. Results: In this meta-analysis, a total of 34 studies (2296 patients) were included out of 1149 retrieved studies. The summarized results showed that the treatment group treated with the combination of 99Tc-MDP and csDMARDs had significantly higher ACR50 (RR = 1.32, 95 % CI: 1.13–1.55, P = 0.0004) and ACR70 (RR = 1.40, 95 % CI: 1.07–1.82, P = 0.01) scores than the control group receiving csDMARDs alone. In addition, the overall incidence of AEs was lower with the combination of 99Tc-MDP and csDMARDs than with csDMARDs alone (RR = 0.75, 95 % CI: 0.60–0.93, P = 0.009), but the possibility of phlebitis was higher in the treatment group (RR = 4.15, 95 % CI: 1.04–16.50, P = 0.04). In addition, the combination of 99Tc-MDP and csDMARDs had advantages over csDMARDs alone in improving DAS28 (WMD = 1.56, 95 % CI: 0.86–2.25, P

Abstract More uncertainty can be obtained when real numbers are extended to intervals. The two new concepts proposed in this work are the natural extensions of cognitive interval information and cognitive uncertain information with real numbered values replaced by interval values. Hence, interval type cognitive interval information and interval type cognitive uncertain information with some characteristics, structures, uncertainty degree functions and score functions of them are analyzed. Two special usages of the two uncertain information types in group decision making show that they have much more algorithmic variations, flexibility and applicability than the mere formal extensions or changes.

Abstract Background Perioperative fluid management during major abdominal surgery has been controversial. Postoperative pancreatic fistula (POPF) is a critical complication of pancreaticoduodenectomy (PD). We conducted a retrospective cohort study to analyze the impact of intraoperative fluid balance on the development of POPF. Methods This retrospective cohort study enrolled 567 patients who underwent open pancreaticoduodenectomy, and the demographic, laboratory, and medical data were recorded. All patients were categorized into four groups according to quartiles of intraoperative fluid balance. Multivariate logistic regression and restricted cubic splines (RCSs) were used to analyze the relationship between intraoperative fluid balance and POPF. Results The intraoperative fluid balance of all patients ranged from -8.47 to 13.56 mL/kg/h. A total of 108 patients reported POPF, and the incidence was 19.0%. After adjusting for potential confounders and using restricted cubic splines, the dose‒response relationship between intraoperative fluid balance and POPF was found to be statistically insignificant. The incidences of bile leakage, postpancreatectomy hemorrhage, and delayed gastric emptying were 4.4%, 20.8%, and 14.8%, respectively. Intraoperative fluid balance was not associated with these abdominal complications. BMI ≥ 25 kg/m2, preoperative blood glucose

Abstract Background Spontaneous spheroid culture is a novel three-dimensional (3D) culture strategy for the rapid and efficient selection of progenitor cells. The objectives of this study are to investigate the pluripotency and differentiation capability of spontaneous spheroids from alveolar bone-derived mesenchymal stromal cells (AB-MSCs); compare the advantages of spontaneous spheroids to those of mechanical spheroids; and explore the mechanisms of stemness enhancement during spheroid formation from two-dimensional (2D) cultured cells. Methods AB-MSCs were isolated from the alveolar bones of C57BL/6 J mice. Spontaneous spheroids formed in low-adherence specific culture plates. The stemness, proliferation, and multi-differentiation capacities of spheroids and monolayer cultures were investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, alkaline phosphatase (ALP) activity, and oil-red O staining. The pluripotency difference between the spontaneous and mechanical spheroids was analyzed using RT-qPCR. Hypoxia-inducible factor (HIFs) inhibition experiments were performed to explore the mechanisms of stemness maintenance in AB-MSC spheroids. Results AB-MSCs successfully formed spontaneous spheroids after 24 h. AB-MSC spheroids were positive for MSC markers and pluripotency markers (Oct4, KLF4, Sox2, and cMyc). Spheroids showed higher Ki67 expression and lower Caspase3 expression at 24 h. Under the corresponding conditions, the spheroids were successfully differentiated into osteogenic and adipogenic lineages. AB-MSC spheroids can induce neural-like cells after neurogenic differentiation. Higher expression of osteogenic markers, adipogenic markers, and neurogenic markers (NF-M, NeuN, and GFAP) was found in spheroids than in the monolayer. Spontaneous spheroids exhibited higher stemness than mechanical spheroids did. HIF-1α and HIF-2α were remarkably upregulated in spheroids. After HIF-1/2α-specific inhibition, spheroid formation was significantly reduced. Moreover, the expression of the pluripotency genes was suppressed. Conclusions Spontaneous spheroids from AB-MSCs enhance stemness and pluripotency. HIF-1/2α plays an important role in the stemness regulation of spheroids. AB-MSC spheroids exhibit excellent multi-differentiation capability, which may be a potent therapy for craniomaxillofacial tissue regeneration.

Srinath, Xie et al. analyze plasma metabolites present in patients with cerebral cavernous angiomas. Cholic acid and hypoxanthine are found in those with Cavernous Angioma disease whilst arachidonic and linoleic acids are found in Cavernous Angioma patients with symptomatic hemorrhage.

This paper presents experimental and numerical studies on the mechanical behavior of 5A90 aluminum-lithium alloy under combined tension and shear loading. Extensive experimental tests under tension and combined loading were conducted, and the influence of material direction, notch radius, and load angle were considered. Based on the test results, the yield strength, ultimate strength, fracture displacement, strain-stress curve, and displacement-stress curve were obtained, discussed, and analyzed. The finite element model (FEM) including fracture behavior was developed, and it was found that the established FEM can well predict the mechanical response of 5A90 aluminum-lithium alloy. Parametric studies were also conducted. Finally, by comparing with the results from FEM (and tests) and predictions from available design codes, the calculation method in Eurocode 9 was suggested to predict the combined strength of 5A90 aluminum-lithium alloy.

Background: The relationship between dental anxiety and mucosal wound healing, especially the inflammatory response, has not been well studied. This study aimed to examine the relationship between anxiety prior to dental treatment and short‐term inflammation following impacted mandibular third molar (IMTM) surgery. Methods: Fifty‐nine patients who required IMTM surgery were recruited for this study. Sample demographics (gender, age) and surgical extent (Pederson classification, duration) were collected. Psychological stress towards surgery was assessed by the Dental Fear Survey (DFS). All surgeries were conducted according to an identical surgical protocol and all patients were given the same medical prescription. Correlations between short‐term inflammation (swelling and trismus after 2 days) and DFS, demographics and surgical extent were statistically analysed. Results: The results showed that patients with a higher DFS score demonstrated more severe swelling (β = 0.36, P = 0.016) and trismus (β = 0.37, P = 0.008) 2 days after surgery. In addition, more severe trismus occurred following more difficult surgery (β = 0.29, P = 0.016) or that with a longer duration (β = 0.21, P = 0.081). Neither gender nor age showed any significant relationship with swelling or trismus. Conclusion: Short‐term inflammatory response following IMTM surgery correlated with the preoperative dental anxiety and this correlation was independent of gender and surgical extent. [ABSTRACT FROM AUTHOR]

The facet joint injection is the most common procedure used to release lower back pain. In this paper, we proposed a deep learning method for detecting and segmenting facet joints in ultrasound images based on convolutional neural networks (CNNs) and enhanced data annotation. In the enhanced data annotation, a facet joint was considered as the first target and the ventral complex as the second target to improve the capability of CNNs in recognizing the facet joint. A total of 300 cases of patients undergoing pain treatment were included. The ultrasound images were captured and labeled by two professional anesthesiologists, and then augmented to train a deep learning model based on the Mask Region-based CNN (Mask R-CNN). The performance of the deep learning model was evaluated using the average precision (AP) on the testing sets. The data augmentation and data annotation methods were found to improve the AP. The AP50 for facet joint detection and segmentation was 90.4% and 85.0%, respectively, demonstrating the satisfying performance of the deep learning model. We presented a deep learning method for facet joint detection and segmentation in ultrasound images based on enhanced data annotation and the Mask R-CNN. The feasibility and potential of deep learning techniques in facet joint ultrasound image analysis have been demonstrated.

Background: At present, the pathogenesis of atherosclerosis has not been fully elucidated, and the diagnosis and treatment face great challenges. Cuproptosis is a novel cell death pattern that might be involved in the development of atherosclerosis. However, no research has reported the correlation between cuproptosis and atherosclerosis. Methods: The differential cuproptosis-related genes (CRGs) between atherosclerosis group and control group (A-CRGs) were discovered via differential expression analysis. The correlation analysis, PPI network analysis, GO, KEGG and GSEA analysis were performed to investigate the function of A-CRGs. The differences of biological function between atherosclerosis group and control group were investigated via immune infiltration analysis and GSVA. The LASSO regression, nomogram and machine learning models were constructed to predict atherosclerosis risk. The atherosclerosis molecular subtypes clusters were discovered via unsupervised cluster analysis. Subsequently, we used the above research methods to analyze the differential CRGs between clusters (M-CRGs) and evaluate the molecular subtypes identification performance of M-CRGs. Finally, we verified the diagnostic value for atherosclerosis and role in cuproptosis of these CRGs through the validation set and in vitro experiments. Results: Five A-CRGs were identified and they were mainly related to the biological function of copper ion metabolism and immune inflammatory response. The diagnostic models and nomogram of atherosclerosis based on 5 A-CRGs indicated that these genes had well diagnostic value. A total of two molecular subtypes clusters were obtained in the atherosclerosis group. There were many differences in biological functions between these two molecular subtypes clusters, such as mitochondrial outer membrane permeabilization and primary immunodeficiency. In addition, 3 M-CRGs were identified in the 2 clusters. Machine learning models and nomogram constructed based on M-CRGs showed that these genes had well molecular subtypes identification efficacy. In the end, the results of in vitro experiment and validation set confirmed the diagnostic value for atherosclerosis and role in cuproptosis of these genes. Conclusion: The cuproptosis may be a potential pathogenesis of atherosclerosis and CRGs may be promising markers for the diagnosis and molecular subtypes identification of atherosclerosis.

Introduction With COVID-19 bringing persistent impact on the worldwide population, perioperative management after SARS-CoV-2 infection needs to be revisited in the new period of different circulating coronavirus variants, vaccination status, increased reinfection rate and new disease control policies. This study aims to explore the association between time to surgery after COVID-19 diagnosis and the risk of postoperative morbidity and mortality.Methods and analysis This is a single-centre ambispective cohort study. Patients with preoperative SARS-CoV-2 infection who require inpatient surgical intervention from 1 December 2022 to 28 February 2023 will be included. Baseline assessment will include the time interval between preoperative SARS-CoV-2 infection and surgery, COVID-19 diagnosis and symptoms, vaccination status and routine preoperative evaluations. The primary outcome will be postoperative composite complications within 30 days after surgery. Association between post-COVID-19 interval and the outcomes will be explored using logistic regression after adjusting for confounding variables.Ethics and dissemination The study protocol has been approved by the Research Ethics Committee of Peking Union Medical College Hospital (IRB K3570). We aim to publish and disseminate the findings in peer-reviewed journals, scientific conferences and on social media.Trial registration number NCT05689840.

Background: The coronavirus disease-2019 (COVID-19) pandemic worldwide has caused a high burden of mental problems, which may be associated with subjective cognitive impairment in the general population. Objectives: This cross-sectional survey aimed to investigate the level and pattern of cognitive failure (CF) and its negative changes during the COVID-19 pandemic among the general population in China. Methods: The participants completed an online questionnaire between April 18 and May 4, 2020, and those aged between 18 and 70 were included in this study. CF was measured using the 14-item CF Questionnaire (CFQ-14). Factors associated with CF and negative changes in CF were evaluated using multiple linear and logistic regression models. A total of 30,879 eligible participants were recruited; most were female (59.10%) and aged 31–45 (61.51%). Results: The mean CFQ-14 score was 15.62 (standard deviation = 11.55), and 4,619 (14.96%) participants reported negative changes in CF during the pandemic. Multiple regression analyses showed that participants with female gender, history of physical and mental disease, the self-perceived influence of COVID-19, altered appetite and taste preference, worse interpersonal relationships, long sleep duration, poor sleep quality, depressive, anxiety and posttraumatic stress disorder symptoms had a higher level of CF and negative CF changes, while regular exercise was associated with a lower risk of both outcomes. Conclusions: This study indicates that CF symptoms should be monitored in the general population during pandemics. A healthy lifestyle and reduction in psychological stress could help promote normal cognitive function during pandemics.

Abstract Background Work-related neck pain (WRNP) is a leading cause of disability and absenteeism. Patients with neck pain often have neck muscle tenderness and decreased cervical mobility, which are sometimes combined with psychosocial issues, such as pain catastrophising, thereby reducing their work ability. Whilst multidisciplinary treatments, including pharmacological interventions, manual therapy and specific neck exercises, have produced positive outcomes, effective personalised treatment modalities are still needed. Furthermore, manual therapies using the hands can bring fatigue to therapist. Occiflex is a computerised device that can provide personalised segmental joint mobilisation based on symptoms and injury of the patient and then provide a medium range of joint activities to improve range of cervical motion. This study aims to compare the effect of computerised mobilisation performed with Occiflex with that of traditional manual therapy on WRNP. Methods We will conduct a prospective randomised controlled trial including 150 patients with WRNP. These patients will be randomly assigned to one of three groups: (i) home exercise (TE), (ii) home exercise plus Occiflex therapy and (iii) home exercise plus manual therapy delivered by a physical therapist. Ten treatment sessions will be performed in four weeks. During the trial, these patients will receive only the assigned treatment and the standard patient education and will be asked not to use any analgesics unless strictly necessary. Assessments by trained evaluators will occur at baseline, week 4 and week 12. The primary outcome measures will include visual analogue scale (VAS) for pain and neck disability index (NDI) at each time point. Secondary outcome measures will include cervical range of motion (CROM), pressure pain threshold (PPT), global perceived effect (GPE) and sick leave. Group by time differences will be analysed using linear mixed models with repeated measures. Discussion This protocol describes the methods for a randomised controlled trial to compare the effectiveness of computerised versus manual mobilisation techniques in treating WRNP. The results will provide an alternative method (Occiflex) that is possibly effective for treating neck pain whilst minimising the manual work done by therapists. Trial registration The study protocol was retrospectively registered at http://www.chictr.org.cn (registration number: ChiCTR2100053076) on November 10, 2021.

Abstract Background Soluble Klotho (S-Klotho) is an anti-aging protein mainly secreted by the kidneys. Hyperuricemia is prevalent among middle-aged and elderly individuals, which affects the development of various chronic diseases. However, there are relatively few studies investigating the association between plasma S-Klotho levels and hyperuricemia in middle-aged and elderly individuals. This study sought to clarify the relationship between S-Klotho and the risk of hyperuricemia in middle-aged and elderly people. Methods During 2007–2016, a total of 50,588 people participated in the National Health and Nutrition Examination Survey. Finally, 12,441 middle-aged and elderly people (aged 40–79) completed the soluble Klotho tests and had obtained complete data. S-Klotho was detected by ELISA kit, and the relationship between S-Klotho and hyperuricemia was assessed by multiple logistic regression. Hyperuricemia is defined as serum uric acid levels higher than or equal to 420 mmol/l in men and 360 mmol/l in women. Results In the middle-aged and elderly, plasma S-Klotho levels were negatively correlated with hyperuricemia, and there was a saturation effect. The inflection point of S-Klotho was 927.8 pg/ml (logarithmic likelihood ratio test = 0.002). When plasma S-Klotho 65 years: Q4 vs Q1, OR (95%CI): 0.72 (0.56, 0.92), P = 0.008)].When the level of S-Klotho was higher, the risk of hyperuricemia in men was lower than that in women [male: Q4 vs Q1, OR (95%CI): 0.67 (0.56, 0.81), P

Cutaneous melanoma is a common cancer and cases have steadily increased since the mid 70s. For some patients, early diagnosis and surgical removal of melanomas is lifesaving, while other patients typically turn to molecular targeted therapies and immunotherapies as treatment options. Easy sampling of melanomas allows the scientific community to identify the most prevalent mutations that initiate melanoma such as the BRAF, NRAS, and TERT genes, some of which can be therapeutically targeted. Though initially effective, many tumors acquire resistance to the targeted therapies demonstrating the need to investigate compensatory pathways. Immunotherapies represent an alternative to molecular targeted therapies. However, inter-tumoral immune cell populations dictate initial therapeutic response and even tumors that responded to treatment develop resistance in the long term. As the protocol for combination therapies develop, so will our scientific understanding of the many pathways at play in the progression of melanoma. The future direction of the field may be to find a molecule that connects all of the pathways. Meanwhile, noncoding RNAs have been shown to play important roles in melanoma development and progression. Studying noncoding RNAs may help us to understand how resistance – both primary and acquired – develops; ultimately allow us to harness the true potential of current therapies. This review will cover the basic structure of the skin, the mutations and pathways responsible for transforming melanocytes into melanomas, the process by which melanomas metastasize, targeted therapeutics, and the potential that noncoding RNAs have as a prognostic and treatment tool.

The segmentation of knee joint is of great significance for diagnosis, guidance and treatment of knee osteoarthritis. However, manual delineation is time-consuming and labor-intensive since various anatomical structures are involved in the 3D MRI volume. Automatic segmentation of the whole knee joint requires no human effort, additionally can improve the quality of arthritis diagnosis and treatment by describing the details more accurately. Existing knee joint segmentation methods in the literature focus on only one or few structures out of many. In this paper, we study the feasibility of knee joint segmentation on MR images based on neural networks and deal with the following challenges: (1) end-to-end segmentation of 15 anatomical structures, including bone and soft tissue, of the whole knee on MR images; (2) robust segmentation of small structures such as the anterior cruciate ligament, accounting for about 0.036% of the volume data. Experiments on the knee joint MR images demonstrate that the average segmentation accuracy of our method achieves 92.92%. The Dice similarity coefficients of 9 structures were above 94%, five structures were between 87% and 90%, and the remaining one was about 76%.

Abstract Adenoid cystic carcinoma (ACC) is an aggressive salivary gland malignancy with limited treatment options for recurrent or metastatic disease. Due to chemotherapy resistance and lack of targeted therapeutic approaches, current treatment options for the localized disease are limited to surgery and radiation, which fails to prevent locoregional recurrences and distant metastases in over 50% of patients. Approximately 20% of patients with ACC carry NOTCH-activating mutations that are associated with a distinct phenotype, aggressive disease, and poor prognosis. Given the role of NOTCH signaling in regulating tumor cell behavior, NOTCH inhibitors represent an attractive potential therapeutic strategy for this subset of ACC. AL101 (osugacestat) is a potent γ-secretase inhibitor that prevents activation of all four NOTCH receptors. While this investigational new drug has demonstrated antineoplastic activity in several preclinical cancer models and in patients with advanced solid malignancies, we are the first to study the therapeutic benefit of AL101 in ACC. Here, we describe the antitumor activity of AL101 using ACC cell lines, organoids, and patient-derived xenograft models. Specifically, we find that AL101 has potent antitumor effects in in vitro and in vivo models of ACC with activating NOTCH1 mutations and constitutively upregulated NOTCH signaling pathway, providing a strong rationale for evaluation of AL101 in clinical trials for patients with NOTCH-driven relapsed/refractory ACC.

Objective(s): Sleep deprivation is a common health problem in modern society and is negatively associated with deleterious effects on cognitive functions such as learning and memory ability. This study was undertaken to provide a detailed account of the effect of chronic ozone intraperitoneal injection on the deleterious effects of sleep deprivation on brain function in rats. Materials and Methods: Sleep deprivation was induced using the modified multiple platform model. The rats received REM sleep deprivation with an intraperitoneal injection of ozone or midazolam for 28 days. The effects of ozone on REM sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by the following approaches: Morris water maze (MWM) tests were used to evaluate spatial learning and memory of rats. Morphological changes in the brain were evaluated using hematoxylin and eosin (HE) staining. RNA-sequence was performed to seek a common mechanism. The expression of the targeted gene was examined by qPCR and Western blotting.Results: Ozone intraperitoneal injection reversed spatial learning and memory deficits associated with REM sleep deprivation, ameliorating pathological brain damage and down-regulating the hippocampal expression of Sema3A in rats after REM sleep deprivation. Conclusion: Ozone intraperitoneal injection alleviated sleep deprivation-induced spatial learning and memory deficits by protecting hippocampal neurons via down-regulation of the expression of Sema3A in the hippocampus.

Abstract Background To compare the safety and efficacy between endoscopic sinus surgery and different biologics in treating chronic rhinosinusitis with nasal polyps in adults by reviewing the existing clinical trials. Methods Data extraction and risk of bias assessment were conducted by 2 independent reviewers according to the PRISMA recommendations and any disagreement was resolved by a third investigator. Outcomes were measured through a random‐effects model. We searched Embase, Web of Science, MEDLINE, Cochrane, and other relevant sources from its inception to April 30, 2022. We included randomized controlled trials(RCTs) involving endoscopic sinus surgery (ESS) or biologics in treating adult patients with chronic rhinosinusitis with nasal polyps. Studies involving other miscellaneous diseases, non‐RCT design, and insufficient participants or follow‐up were excluded. Results In this systematic review, five RCTs and 1748 patients were included. All the biologics, as well as ESS, could significantly improve key nasal outcomes in CRSwNP both at 6 months and 1 year. Dupilumab exhibited better efficacy than ESS in improving SNOT‐22 scores at one year. However, ESS showed superiority over three biologics in improving nasal congestion scores (NCS) at two various time points, except for better efficacy of Dupilumab at 1 year. For the loss of smell scores, a greater improvement was observed in the Dupilumab cohort compared with other biologics and even ESS counterparts. Safety analysis showed no significant difference between the ESS cohort and biologic treatment. Conclusions In summary, ESS showed comparable improvement in quality of life and symptoms to Omalizumab, Mepolizumab, and Benralizumab. Dupilumab seems to be more effective than ESS in selected items, whereas head‐to‐head trials and real‐world studies are urgent to compare their efficacy. Our findings also showed that biologics could be applied as alternative or adjuvant therapy for uncontrolled severe CRSwNP.