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ImportanceOxidative stress contributes to the progression of non-alcoholic fatty liver disease (NAFLD). Antioxidants from food can reduce NAFLD incidence, and the Composite Dietary Antioxidant Index (CDAI) measures total antioxidant capacity (TAC). However, the relationship between CDAI and NAFLD in the US adult population remains unclear.ObjectiveTo assess whether CDAI is associated with NAFLD in US adults.Design, setting, and participantsThis population-based cross-sectional study used data on US adults from the National Health and Nutrition Examination Survey (NHANES) 2005–2016 cycles. Data were analyzed from January to February 2024.ExposuresCDAI obtained from the dietary intake questionnaire.Main outcomes and measuresThe main outcome was NAFLD which defined by the US fatty liver score (USFLI) ≥30. Sampling weights were calculated according to NHANES guidelines.ResultsAmong 9,746 adults included in this study [mean age, 48.3 years; 4,662 (47.6%) males], 3,324 (33.0%) were classified as having NAFLD using USFLI. In the fully adjusted of multivariable logistic regression, CDAI was negatively associated with NAFLD (odds ratio [OR], 0.95; 95% CI, 0.93–0.98). Furthermore, individuals in the highest quartile of CDAI were 34% less likely to have NAFLD compared to those in the lowest quartile (OR, 0.66; 95% CI, 0.52–0.85). In subgroup analyses, CDAI was inversely associated with NAFLD among participants with a BMI

BackgroundIn China, Atractylodes-containing Chinese medicines are widely used as adjuvant therapy to neoadjuvant chemotherapy (NAC) in individuals diagnosed with advanced gastric cancer (AGC). Nevertheless, the findings concerning its effectiveness are still restricted. The aim from this research was to examine the efficiency and security Atractylodes macrocephala-containing traditional Chinese medicine together with NAC in the management of AGC.MethodsLiterature was systematically searched across 8 electronic databases until September 20, 2023. Two researchers conducted a thorough review of the selected studies. The primary outcome measures included the objective response rate (ORR), disease control rate (DCR), quality of life (QOL), adverse drug reactions (ADRs), and levels of peripheral blood lymphocytes. The relevant effect estimates are as follows as risk ratios (RR) or mean differences (MD) with corresponding 95% confidence intervals (CI). Credibility of information was evaluated using the GRADE analyzer.ResultsThe results showed that solely on the basis of the accessible literature examined in NAC patients, individuals who received the therapeutic regimen containing Atractylodis Macrocephalae Chinese herbal preparations demonstrated a superior overall response rate (Relative Risk: 1.41, 95% confidence interval: 1.27-1.57, P < 0.001); DCR (RR: 1.20, 95% confidence interval: 1.13-1.27, P < 0.001), as compared to QOL (RR: 1.43, 95% confidence interval: 1.30-1.57, P < 0.001, MD: 8.47, 95% confidence interval: 7.16 - 9.77, P < 0.001); the proportions of CD3+ T-cells, CD4+ T-cells, CD8+ T-cells, CD4+CD8+ T-cells were increased; and the incidence of adverse reactions was decreased. Subgroup analyses showed that oral administration of all the traditional Chinese medicines containing Atractylodes macrocephala could improve tumor efficacy. Regardless of the duration of therapy of ≥8 weeks or

BackgroundDue to the rising standard of living and advances in public health and medical care in recent years in China, the health-related quality of life (HRQoL) has been increasingly acknowledged as an important part of health management of adults. This study aimed to analyze the HRQoL of Chinese adults and identify the influencing factors, proposing specific recommendations for improvement.MethodsA cross-sectional study was conducted among 1,291 selected adults from four provinces spanning different regions in China aged ≥18 years from July 2021 and January 2022. The EuroQol-5D-5L (EQ-5D-5L) was used to conduct the HRQoL survey, and a general questionnaire was administered to collect demographic characteristics, general information, and health behaviors of participants. The health utility value was measured, and one-way analysis of variance was performed. The Tobit regression model was employed to analyze the factors influencing the HRQoL of Chinese adults.ResultsThe mean health utility values and visual analog scale scores for adults were 0.9400 ± 0.1197 and 84.09 ± 14.392, respectively. Notably, 60.3% of respondents reported no difficulties in any of the five dimensions of EQ-5D. However, a substantial proportion faced challenges in anxiety/depression (27%) and pain/discomfort (26.2%). Tobit regression model revealed that age, marital status, educational level, diet, sleep, mental state, mood, and chronic diseases significantly impact the HRQoL of Chinese adults.ConclusionThe HRQoL among Chinese adults is generally satisfactory, but pay particular attention on areas such as pain, psychological anxiety, chronic diseases, and negative emotions is needed. The factors such as stress associated with marriage and the demands of high-skilled occupations might influence the overall health of the population. According to our findings, public health strategies to improve HRQoL should be developed to promote relatively healthy environments and lifestyles for older adults. Moreover, proactive measures are crucial for mitigating the potential health impacts associated with marital stress and high-skilled employment.

This review offered a comprehensive analysis of tendon and ligament injuries, emphasizing the crucial role of tendon-derived stem cells (TDSCs) in tissue engineering as a potential solution for these challenging medical conditions. Tendon and ligament injuries, prevalent among athletes, the elderly, and laborers, often result in long-term disability and reduced quality of life due to the poor intrinsic healing capacity of these avascular structures. The formation of biomechanically inferior scar tissue and a high rate of reinjury underscore the need for innovative approaches to enhance and guide the regenerative process. This review delved into the complexities of tendon and ligament structure and function, types of injuries and their impacts, and the limitations of the natural repair process. It particularly focused on the role of TDSCs within the context of tissue engineering. TDSCs, with their ability to differentiate into tenocytes, are explored in various applications, including biocompatible scaffolds for cell tracking, co-culture systems to optimize tendon-bone healing, and graft healing techniques. The review also addressed the challenges of immunoreactivity post-transplantation, the importance of pre-treating TDSCs, and the potential of hydrogels and decellularized matrices in supporting tendon regeneration. It concluded by highlighting the essential roles of mechanical and molecular stimuli in TDSC differentiation and the current challenges in the field, paving the way for future research directions.

Tigecycline is a last-resort drug used to treat serious infections caused by multidrug-resistant bacteria. tet(X4) is a recently discovered plasmid-mediated tigecycline resistance gene that confers high-level resistance to tigecycline and other tetracyclines. Since the first discovery of tet(X4) in 2019, it has spread rapidly worldwide, and as a consequence, tigecycline has become increasingly ineffective in the clinical treatment of multidrug-resistant infections. In this study, we identified and analyzed tet(X4)-positive Escherichia coli isolates from duck farms in Hunan Province, China. In total, 976 samples were collected from nine duck farms. Antimicrobial susceptibility testing and whole-genome sequencing (WGS) were performed to establish the phenotypes and genotypes of tet(X4)-positive isolates. In addition, the genomic characteristics and transferability of tet(X4) were determined based on bioinformatics analysis and conjugation. We accordingly detected an E. coli strain harboring tet(X4) and seven other resistance genes in duck feces. Multi-locus sequence typing analysis revealed that this isolate belonged to a new clone, and subsequent genetic analysis indicated that tet(X4) was carried in a 4608-bp circular intermediate, flanked by ISVsa3-ORF2-abh elements. Moreover, it exhibited transferability to E. coli C600 with a frequency of 10-5. The detection of tet(X4)-harboring E, coli strains on duck farms enhances our understanding of tigecycline resistance dynamics. The transferable nature of the circular intermediate of tet(X4) contributing to the spread of tigecycline resistance genes poses a substantial threat to healthcare. Consequently, vigilant monitoring and proactive measures are necessary to prevent their spread.

IntroductionThe uridine diphosphate (UDP)-glycosyltransferase (UGT) family is the largest glycosyltransferase family, which is involved in the biosynthesis of natural plant products and response to abiotic stress. UGT has been studied in many medicinal plants, but there are few reports on Platycodon grandiflorus. This study is devoted to genome-wide analysis of UGT family and identification of UGT genes involved in drought stress of Platycodon grandiflorus (PgUGTs).MethodsThe genome data of Platycodon grandiflorus was used for genome-wide identification of PgUGTs, online website and bioinformatics analysis software was used to conduct bioinformatics analysis of PgUGT genes and the genes highly responsive to drought stress were screened out by qRT-PCR, these genes were cloned and conducted bioinformatics analysis.ResultsA total of 75 PgUGT genes were identified in P.grandiflorus genome and clustered into 14 subgroups. The PgUGTs were distributed on nine chromosomes, containing multiple cis-acting elements and 22 pairs of duplicate genes were identified. Protein-protein interaction analysis was performed to predict the interaction between PgUGT proteins. Additionally, six genes were upregulated after 3d under drought stress and three genes (PGrchr09G0563, PGrchr06G0523, PGrchr06G1266) responded significantly to drought stress, as confirmed by qRT-PCR. This was especially true for PGrchr06G1266, the expression of which increased 16.21-fold after 3d of treatment. We cloned and conducted bioinformatics analysis of three candidate genes, both of which contained conserved motifs and several cis-acting elements related to stress response, PGrchr06G1266 contained the most elements.DiscussionPgGT1 was confirmed to catalyze the C-3 position of platycodin D and only eight amino acids showed differences between gene PGr008G1527 and PgGT1, which means PGr008G1527 may be able to catalyze the C-3 position of platycodin D in the same manner as PgGT1. Seven genes were highly expressed in the roots, stems, and leaves, these genes may play important roles in the development of the roots, stems, and leaves of P. grandiflorus. Three genes were highly responsive to drought stress, among which the expression of PGrchr06G1266 was increased 16.21-fold after 3d of drought stress treatment, indicating that PGrchr06G1266 plays an important role in drought stress tolerance. To summarize, this study laied the foundation to better understand the molecular bases of responses to drought stress and the biosynthesis of platycodin.

BackgroundGallbladder neuroendocrine neoplasms (GB-NENs) are a rare malignant disease, with most cases diagnosed at advanced stages, often resulting in poor prognosis. However, studies regarding the prognosis of this condition and its comparison with gallbladder adenocarcinomas (GB-ADCs) have yet to yield convincing conclusions.MethodsWe extracted cases of GB-NENs and GB-ADCs from the Surveillance, Epidemiology, and End Results (SEER) database in the United States. Firstly, we corrected differences in clinical characteristics between the two groups using propensity score matching (PSM). Subsequently, we visualized and compared the survival outcomes of the two groups using the Kaplan-Meier method. Next, we employed the least absolute shrinkage and selection operator (LASSO) regression and Cox regression to identify prognostic factors for GB-NENs and constructed two nomograms for predicting prognosis. These nomograms were validated with an internal validation dataset from the SEER database and an external validation dataset from a hospital. Finally, we categorized patients into high-risk and low-risk groups based on their overall survival (OS) scores.ResultsA total of 7,105 patients were enrolled in the study, comprising 287 GB-NENs patients and, 6,818 GB-ADCs patients. There were substantial differences in clinical characteristics between patients, and GB-NENs exhibited a significantly better prognosis. Even after balancing these differences using PSM, the superior prognosis of GB-NENs remained evident. Independent prognostic factors selected through LASSO and Cox regression were age, histology type, first primary malignancy, tumor size, and surgery. Two nomograms for prognosis were developed based on these factors, and their performance was verified from three perspectives: discrimination, calibration, and clinical applicability using training, internal validation, and external validation datasets, all of which exhibited excellent validation results. Using a cutoff value of 166.5 for the OS nomogram score, patient mortality risk can be identified effectively.ConclusionPatients with GB-NENs have a better overall prognosis compared to those with GB-ADCs. Nomograms for GB-NENs prognosis have been effectively established and validated, making them a valuable tool for assessing the risk of mortality in clinical practice.

Background: Breast squamous cell carcinoma (SCC) is an uncommon and highly aggressive variant of metaplastic breast cancer. Despite its rarity, there is currently no consensus on treatment guidelines for this specific subtype. Previous studies have demonstrated that chemotherapy alone has limited efficacy in treating breast SCC. However, the potential for targeted therapy in combination with chemotherapy holds promise for future treatment options.Case presentation: In this case report, we present a patient with advanced HER2-positive breast SCC, exhibiting a prominent breast mass, localized ulcers, and metastases in the lungs and brain. Our treatment approach involved the administration of HER2-targeted drugs in conjunction with paclitaxel, resulting in a sustained control of tumor growth.Conclusion: This case represents a rare occurrence of HER2-positive breast SCC, with limited available data on the efficacy of previous HER2-targeted drugs in treating such patients. Our study presents the first application of HER2-targeted drugs in this particular case, offering novel therapeutic insights for future considerations. Additionally, it is imperative to conduct further investigations to assess the feasibility of treatment options in a larger cohort of patients.

Plants offer a promising platform for cost-effective production of biologically active therapeutic glycoproteins. In previous studies, we have developed a plant expression system based on Bamboo mosaic virus (BaMV) by incorporating secretory signals and an affinity tag, which resulted in notably enhanced yields of soluble and secreted fusion glycoproteins (FGs) in Nicotiana benthamiana. However, the presence of fusion tags on recombinant glycoproteins is undesirable for biomedical applications. This study aimed to develop a refined expression system that can efficiently produce tag-free glycoproteins in plants, with enhanced efficacy of mature interferon gamma (mIFNγ) against viruses. To accommodate the specific requirement of different target proteins, three enzymatically or chemically cleavable linkers were provided in this renovated BaMV-based expression system. We demonstrated that Tobacco etch virus (TEV) protease could process the specific cleavage site (LTEV) of the fusion protein, designated as SSExtHis(SP)10LTEV-mIFNγ, with optimal efficiency under biocompatible conditions to generate tag-free mIFNγ glycoproteins. The TEV protease and secretory-affinity tag could be effectively removed from the target mIFNγ glycoproteins through Ni2+-NTA chromatography. In addition, the result of an antiviral assay showed that the tag-free mIFNγ glycoproteins exhibited enhanced biological properties against Sindbis virus, with comparable antiviral activity of the commercialized HEK293-expressed hIFNγ. Thus, the improved BaMV-based expression system developed in this study may provide an alternative strategy for producing tag-free therapeutic glycoproteins intended for biomedical applications.

Multi-robot cooperative control has been extensively studied using model-based distributed control methods. However, such control methods rely on sensing and perception modules in a sequential pipeline design, and the separation of perception and controls may cause processing latencies and compounding errors that affect control performance. End-to-end learning overcomes this limitation by implementing direct learning from onboard sensing data, with control commands output to the robots. Challenges exist in end-to-end learning for multi-robot cooperative control, and previous results are not scalable. We propose in this article a novel decentralized cooperative control method for multi-robot formations using deep neural networks, in which inter-robot communication is modeled by a graph neural network (GNN). Our method takes LiDAR sensor data as input, and the control policy is learned from demonstrations that are provided by an expert controller for decentralized formation control. Although it is trained with a fixed number of robots, the learned control policy is scalable. Evaluation in a robot simulator demonstrates the triangular formation behavior of multi-robot teams of different sizes under the learned control policy.

Cytokines are involved in neural homeostasis and pathological processes associated with neuroinflammation after spinal cord injury (SCI). The biological effect of cytokines, including those associated with acute or chronic SCI pathologies, are the result of receptor-mediated signaling through the Janus kinases (JAKs) as well as the signal transducers and activators of transcription (STAT) DNA-binding protein families. Although therapies targeting at cytokines have led to significant changes in the treatment of SCI, they present difficulties in various aspects for the direct use by patients themselves. Several small-molecule inhibitors of JAKs, which may affect multiple pro-inflammatory cytokine-dependent pathways, as well as STATs, are in clinical development for the treatment of SCI. This review describes the current understanding of the JAK-STAT signaling in neuroendocrine homeostasis and diseases, together with the rationale for targeting at this pathway for the treatment of SCI.

ObjectiveTo compare the ultrasound guidance and traditional methods in femoral artery puncture.MethodsWe searched the databases to evaluate the rate of success on first attempt and the incidence of hematoma. The random effects model was used for performing a meta-analysis to estimate the odds ratio (ORs), mean difference (MD), and 95% confidence interval (CI).ResultsA total of nine articles including 2,361 patients were included in this meta-analysis. The rate of success on first attempt were 79.6% (1,289/1,619) and 54.1% (883/1,644) in patients of the ultrasound group and traditional method group, respectively [OR = 3.14 (95% CI = 2.30–4.28), combined OR value Z = 7.23 (P

Tuberculous meningitis (TBM) is the most common form of central nervous system tuberculosis (TB) and the most severe form of extrapulmonary TB. It often presents with non-specific symptoms initially and has a high mortality and disability rate. With good central nervous system penetration, linezolid is recommended for treating drug-resistant, severe, or refractory tuberculous meningitis in China. Despite the benefits of linezolid on TBM treatment, the adverse effects of long-term therapy, such as myelosuppression, peripheral neuritis, and optic neuritis, are notable and can be severe and even life-threatening, leading to discontinuation and compromising treatment expectations. Contezolid is a novel oxazolidinone antibacterial agent approved by the National Medical Products Administration of China in 2021, which has a more favorable safety profile than linezolid in terms of myelosuppression and monoamine oxidase inhibition. Here we first report a case of TBM in a patient who was intolerant to antituberculosis treatment with linezolid and achieved good efficacy and safety results after the compassionate use of contezolid. Given the widespread use of linezolid in TB treatment and the potential risks for long-term use, multi-center prospective controlled clinical trials in TB and TBM patients are needed to investigate the appropriate use of contezolid further.

Severe spinal cord injuries (SCIs) usually result in the temporary or permanent impairment of strength, sensation or autonomic functions below the sites of injuries. To date, a large number of therapeutic approaches have been used to ameliorate SCIs, and subsequent stem cell transplantation appears to be a promising strategy. The aim of this study was to evaluate the therapeutic effect of stem cells by changes in the evoked potentials at different time points after a transplantation of spermatogonial stem cells (SSCs) to differentiate the source neurons in a rat model with SCIs, as well as through histopathology. A modified Plemel spinal cord lateral compression model was used. The experiment was divided into a blank, a control and a SSC transplantation group. Motor activity scores, sensory evoked potentials (SEPs) and motor evoked potentials (MEPs) were assessed through motor resuscitation as well as histologic evaluation on each experimental group to determine the improvement. Consistent with our results, motor scores and evoked potentials were significantly improved in the SSC transplantation group. In addition, a histologic assessment showed that the transplanted stem cells had a significant restorative effect on the reconstruction of tissue cells. 1 week after the stem cell transplantation, the SSC transplantation group showed improvement in spinal cord functions and spinal cord pathologic injuries. After 2 weeks and beyond, the SSC transplantation group showed significant improvement in spinal cord functions and spinal cord pathology compared to the control group, meanwhile the evoked potentials and motor function of the hind limbs of rats in the SSC transplantation group were significantly improved. Therefore, the therapeutic strategies for spermatogonial stem cells will be an effective program in the study on SCIs, and we suggest the somatosensory evoked potentials as a tool to assess the degree of recovery from SCIs after the transplantation of stem cells.

Ongoing warming and sea-ice reductions in the Arctic can seriously impact cold-water species, such as polar cod (Boreogadus saida), necessitating biomonitoring to reveal the ecological consequences. Recent methodological advancements in environmental DNA (eDNA) techniques have increased our ability to conduct ecological monitoring at various locations, including the Arctic. This study aimed to provide an overview of the distribution of polar cod across the Bering and Chukchi Seas by employing species-specific detection of eDNA. First, we successfully developed novel species-specific qPCR assay targeting the mitochondrial D-loop region, which exclusively amplifies eDNA derived from polar cod. Subsequently, polar cod eDNA was detected using the assay from the samples that we collected latitudinally across the study area during the open-water season. Polar cod eDNA was primarily detected in the surface water from the central Chukchi Sea shelf and the northernmost observation line (75°N), which was located on the shelf slope, off the Point Barrow, and in the marginal ice zone. In contrast, only trace amounts of eDNA were detected in the Bering Sea. This pattern corresponded well with the distribution of water masses classified based on environmental conditions. The detection of eDNA in surface water was clearly limited to cold (-1 to 5°C) and low salinity (25–32) water, whereas it was detected in a higher salinity range (32–34) in the middle and bottom layers. These findings are consistent with current knowledge about the distribution and habitat of the polar cod, suggesting that eDNA can be regarded as a reliable tool to replace or supplement conventional methods. Incorporating eDNA techniques into large-scale oceanographic surveys can improve the spatial and temporal resolution of fish species detection with a reasonable sampling effort and will facilitate the continuous monitoring of Arctic ecosystems.

Introduction: BuShen HuoXue (BSHX) decoction is commonly used in the clinical treatment of premature ovarian failure because it can increase estradiol level and decrease follicle-stimulating hormone level. In this study, we determined the potential therapeutic effects of BSHX decoction via anti-stress pathway and the underlying mechanism by using the nematode Caenorhabditis elegans as an assay system.Methods: Bisphenol A (BPA, 175 μg/mL) was used to establish a fertility-defective C. elegans model. Nematodes were cultivated according to standard methods. Brood size, DTC, the number of apoptotic cells and oocytes were used to evaluate the fertility of nematodes. Nematodes were cultivated at 35°C as heat stress. RNA isolation and RT-qPCR were used to detect the mRNA expression level of genes. Intestinal ROS and intestinal permeability were used to evaluate the function of intestinal barrier. BSHX decoction was extracted with water and analyzed by LC/Q-TOF.Results and Discussion: In BPA-treated N2 nematodes, 62.5 mg/mL BSHX decoction significantly improved the brood size and the oocytes quality at different developmental stages. BSHX decoction improved resistance to heat stress through the hsf-1-mediated heat-shock signaling pathway. Further analysis showed that the decoction significantly improved the transcriptional levels of hsf-1 downstream target genes, such as hsp-16.1, hsp-16.2, hsp-16.41, and hsp-16.48. Other than hsp-16.2 expression in the gonad, the decoction also affected intestinal hsp-16.2 expression and significantly reversed the adverse effects induced by BPA. Moreover, the decoction ameliorated intestinal ROS and permeability. Thus, BSHX decoction can improve fertility by increasing intestinal barrier function via hsp-16.2-mediated heat-shock signaling pathway in C. elegans. These findings reveal the underlying regulatory mechanisms of hsp-16.2-mediated heat resistance against fertility defect.

Autofluorescence is frequently observed in animal tissues, interfering with an experimental analysis and leading to inaccurate results. Sudan black B (SBB) is a staining dye widely used in histological studies to eliminate autofluorescence. In this study, our objective was to characterize brain tissue autofluorescence present in three models of acute brain injury, including collagenase-induced intracerebral hemorrhage (ICH), traumatic brain injury (TBI), and middle cerebral artery occlusion, and to establish a simple method to block autofluorescence effectively. Using fluorescence microscopy, we examined autofluorescence in brain sections affected by ICH and TBI. In addition, we optimized a protocol to block autofluorescence with SBB pretreatment and evaluated the reduction in fluorescence intensity. Compared to untreated, pretreatment with SBB reduced brain tissue autofluorescence in the ICH model by 73.68% (FITC), 76.05% (Tx Red), and 71.88% (DAPI), respectively. In the TBI model, the ratio of pretreatment to untreated decreased by 56.85% (FITC), 44.28% (Tx Red), and 46.36% (DAPI), respectively. Furthermore, we tested the applicability of the protocol using immunofluorescence staining or Cyanine-5.5 labeling in the three models. SBB treatment is highly effective and can be applied to immunofluorescence and fluorescence label imaging techniques. SBB pretreatment effectively reduced background fluorescence but did not significantly reduce the specific fluorescence signal and greatly improved the signal-to-noise ratio of fluorescence imaging. In conclusion, the optimized SBB pretreatment protocol blocks brain section autofluorescence of the three acute brain injury models.

IntroductionThe lateral habenula (LHb) is a promising deep brain stimulation (DBS) target for treatment-resistant depression (TRD). However, the optimal surgical trajectory and its safety of LHb DBS are lacking.MethodsWe reported surgical trajectories for the LHb in six TRD patients treated with DBS at the General Hospital of the Chinese People's Liberation Army between April 2021 and May 2022. Pre-operative fusions of magnetic resonance imaging (MRI) and computed tomography (CT) were conducted to design the implantation trajectory of DBS electrodes. Fusions of MRI and CT were conducted to assess the safety or precision of LHb DBS surgery or implantable electrodes locations.ResultsResults showed that the optimal entry point was the posterior middle frontal gyrus. The target coordinates (electrode tips) were 3.25 ± 0.82 mm and 3.25 ± 0.82 mm laterally, 12.75 ± 0.42 mm and 13.00 ± 0.71 mm posterior to the midpoint of the anterior commissure–posterior commissure (AC-PC) line, and 1.83 ± 0.68 mm and 1.17 ± 0.75 mm inferior to the AC-PC line in the left and right LHb, respectively. The “Ring” angles (relative to the AC-PC level on the sagittal section plane) of the trajectories to the left and right LHb were 51.87° ± 6.67° and 52.00° ± 7.18°, respectively. The “Arc” angles (relative to the midline of the sagittal plane) were 33.82° ± 3.39° and 33.55° ± 3.72°, respectively. Moreover, there was small deviation of actual from planned target coordinates. No patient had surgery-, disease- or device-related adverse events during the perioperative period.ConclusionOur results suggested that LHb-DBS surgery via frontal trajectory is safe, accurate, and feasible. This is an applicable work to report in detail the target coordinates and surgical path of human LHb-DBS. It has of great clinical reference value to treat more cases of LHb-DBS for TRD.

BackgroundThe addition of bevacizumab was found to be associated with prolonged survival whether in combination with chemotherapy, tyrosine kinase inhibitors or immune checkpoint inhibitors in the treatment landscape of advanced non-small cell lung cancer (NSCLC) patients. However, the biomarkers for efficacy of bevacizumab were still largely unknown. This study aimed to develop a deep learning model to provide individual assessment of survival in advanced NSCLC patients receiving bevacizumab.MethodsAll data were retrospectively collected from a cohort of 272 radiological and pathological proven advanced non-squamous NSCLC patients. A novel multi-dimensional deep neural network (DNN) models were trained based on clinicopathological, inflammatory and radiomics features using DeepSurv and N-MTLR algorithm. And concordance index (C-index) and bier score was used to demonstrate the discriminatory and predictive capacity of the model.ResultsThe integration of clinicopathologic, inflammatory and radiomics features representation was performed using DeepSurv and N-MTLR with the C-index of 0.712 and 0.701 in testing cohort. And Cox proportional hazard (CPH) and random survival forest (RSF) models were also developed after data pre-processing and feature selection with the C-index of 0.665 and 0.679 respectively. DeepSurv prognostic model, indicated with best performance, was used for individual prognosis prediction. And patients divided in high-risk group were significantly associated with inferior PFS (median PFS: 5.4 vs 13.1 months, P

The field of cancer neoantigen investigation has developed swiftly in the past decade. Predicting novel and true neoantigens derived from large multi-omics data became difficult but critical challenges. The rise of Artificial Intelligence (AI) or Machine Learning (ML) in biomedicine application has brought benefits to strengthen the current computational pipeline for neoantigen prediction. ML algorithms offer powerful tools to recognize the multidimensional nature of the omics data and therefore extract the key neoantigen features enabling a successful discovery of new neoantigens. The present review aims to outline the significant technology progress of machine learning approaches, especially the newly deep learning tools and pipelines, that were recently applied in neoantigen prediction. In this review article, we summarize the current state-of-the-art tools developed to predict neoantigens. The standard workflow includes calling genetic variants in paired tumor and blood samples, and rating the binding affinity between mutated peptide, MHC (I and II) and T cell receptor (TCR), followed by characterizing the immunogenicity of tumor epitopes. More specifically, we highlight the outstanding feature extraction tools and multi-layer neural network architectures in typical ML models. It is noted that more integrated neoantigen-predicting pipelines are constructed with hybrid or combined ML algorithms instead of conventional machine learning models. In addition, the trends and challenges in further optimizing and integrating the existing pipelines are discussed.

Low back pain (LBP) is one of the most common musculoskeletal symptoms and severely affects patient quality of life. The majority of people may suffer from LBP during their life-span, which leading to huge economic burdens to family and society. According to the series of the previous studies, intervertebral disc degeneration (IDD) is considered as the major contributor resulting in LBP. Furthermore, non-coding RNAs (ncRNAs), mainly including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), can regulate diverse cellular processes, which have been found to play pivotal roles in the development of IDD. However, the potential mechanisms of action for ncRNAs in the processes of IDD are still completely unrevealed. Therefore, it is challenging to consider ncRNAs to be used as the potential therapeutic targets for IDD. In this paper, we reviewed the current research progress and findings on ncRNAs in IDD: i). ncRNAs mainly participate in the process of IDD through regulating apoptosis of nucleus pulposus (NP) cells, metabolism of extracellular matrix (ECM) and inflammatory response; ii). the roles of miRNAs/lncRNAs/circRNAs are cross-talk in IDD development, which is similar to the network and can modulate each other; iii). ncRNAs have been attempted to combat the degenerative processes and may be promising as an efficient bio-therapeutic strategy in the future. Hence, this review systematically summarizes the principal pathomechanisms of IDD and shed light on the therapeutic potentials of ncRNAs in IDD.

ObjectiveTo evaluate performance of the ABC (Age, Biomarkers, Clinical history)-bleeding risk score in estimating major bleeding risk in Chinese patients with atrial fibrillation (AF) on oral anticoagulation (OAC) therapy in real-world practice.MethodsData were collected from the Chinese Atrial Fibrillation Registry study (CAFR). Patients were stratified into low-, medium-, and high-risk groups based on ABC-bleeding risk score with 1-year major bleeding risk ( 2%) and modified HAS-BLED score (≤1, 2, and > 2 points). Cox proportional-hazards (Cox-PH) models were used to determine the association of major bleeding incidence with bleeding scores. Harrell’s C-index of the two scores were compared. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) at 1 year were employed to evaluate the reclassification capacity. The calibration curve was plotted to compare the predicted major bleeding risk using ABC-bleeding risk score with the observed annualized event rate. The decision analysis curves (DCA) were performed to show the clinical utilization of two scores in identifying major bleeding events.ResultsThe study included 2,892 AF patients on OAC therapy. After the follow-up of 3.0 years, 48 patients had major bleeding events; the incidence of a bleeding event in the low-, medium-, and high-risk groups according to ABC-bleeding risk score was 0.31% (reference group, HR = 1.00),0.51% (HR = 1.83, 95%CI: 0.91–3.69, P = 0.09), and 1.49% (HR = 4.92, 95%CI: 2.34–10.30, P < 0.001), respectively. Major bleeding incidence had an independent association with growth differentiation factor 15 (GDF-15) level (HR = 2.16, 95%CI: 1.27–3.68, P = 0.005) after adjusting components of the HAS-BLED score and cTnT-hs level. The ABC-bleeding score showed a Harrell’s C-index of 0.67 (95%CI: 0.60–0.75) in estimating major bleeding risk, which was non-significant compared to the modified HAS-BLED score (0.67 vs. 0.63; P = 0.38). NRI and IDI also revealed comparable reclassification capacity of ABC-bleeding risk score compared with HAS-BLED score (14.6%, 95%CI: −10.2%, 39.4%, P = 0.25; 0.2%, 95%CI −0.1 to 0.9%, P = 0.64). Cross-tabulation of the two scores showed that the ABC-bleeding score outperformed the HAS-BLED score in identifying patients with a high risk of major bleeding. The calibration curve showed that the ABC-bleeding risk score overestimated the observed major bleeding risk. DCA did not show any difference in net benefit when using either of the scores.ConclusionThis study verified the value of the ABC-bleeding risk score in assessing major bleeding risk in Chinese patients with AF on OAC therapy in real-world practice. Despite the overestimation of major bleeding risk, ABC-bleeding score performed better in stratifying patients with a high risk than the modified HAS-BLED score. Combining the two scores could be a clinically practical strategy for precisely stratifying AF patients, especially those at a high risk of major bleeding, and further supporting the optimization of OAC treatment.

BackgroundTraumatic spinal cord injuries (TSCIs) are worldwide public health problems that are difficult to cure and impose a substantial economic burden on society. There has been a lack of extensive multicenter review of TSCI epidemiology in northwest China during the Corona Virus Disease 2019 (COVID-19) pandemic.MethodA multicenter retrospective study of 14 selected hospitals in two provinces in northwest China was conducted on patients admitted for TSCI between 2017 and 2020. Variables assessed included patient demographics, etiology, segmental distribution, treatment, waiting time for treatment, and outcomes.ResultsThe number of patients with TSCI showed an increasing trend from 2017 to 2019, while there were 12.8% fewer patients in 2020 than in 2019. The male-to-female ratio was 3.67:1, and the mean age was 48 ± 14.9 years. The primary cause of TSCI was high falls (38.8%), slip falls/low falls (27.7%), traffic accidents (23.9%), sports (2.6%), and other factors (7.0%). The segmental distribution showed a bimodal pattern, peak segments were C6 and L1 vertebra, L1 (14.7%), T12 (8.2%), and C6 (8.2%) were the most frequently injured segments. In terms of severity, incomplete injury (72.8%) occurred more often than complete injury (27.2%). The American Spinal Injury Association impairment scale of most patients did not convert before and after treatment in the operational group (71.6%) or the conservative group (80.6%). A total of 975 patients (37.2%) from urban and 1,646 patients (62.8%) from rural areas were included; almost all urban residents could rush to get treatment after being injured immediately (

BackgroundA few intracranial lesions may present only with positional vertigo which are very easy to misdiagnose as benign paroxysmal positional vertigo (BPPV); the clinicians should pay more attention to this disease.ObjectivesTo analyze the clinical characteristics of 6 patients with intracranial tumors who only presented with positional vertigo to avoid misdiagnosing the disease.Material and methodsSix patients with intracranial tumors who only presented with positional vertigo treated in our clinic between May 2015 to May 2019 were reviewed, and the clinical symptoms, features of nystagmus, imaging presentation, and final diagnosis of the patients were evaluated.ResultsAll patients presented with positional vertigo and positional nystagmus induced by the changes in head position or posture, including one case with downbeating nystagmus in a positional test, two cases with left-beating nystagmus, one case with apogeotropic nystagmus in a roll test, one case with right-beating nystagmus, and one case with left-beating and upbeating nystagmus. Brain MRI showed the regions of the tumors were in the vermis of the cerebellum, the fourth ventricle, the lateral ventricle, and the cerebellar hemisphere.

Background: In China, Atractylodes-containing Chinese medicines are widely used as adjuvant therapy to neoadjuvant chemotherapy (NAC) in individuals diagnosed with advanced gastric cancer (AGC). Nevertheless, the findings concerning its effectiveness are still restricted. The aim from this research was to examine the efficiency and security Atractylodes macrocephala-containing traditional Chinese medicine together with NAC in the management of AGC. Methods: Literature was systematically searched across 8 electronic databases until September 20, 2023. Two researchers conducted a thorough review of the selected studies. The primary outcome measures included the objective response rate (ORR), disease control rate (DCR), quality of life (QOL), adverse drug reactions (ADRs), and levels of peripheral blood lymphocytes. The relevant effect estimates are as follows as risk ratios (RR) or mean differences (MD) with corresponding 95% confidence intervals (CI). Credibility of information was evaluated using the GRADE analyzer. Results: The results showed that solely on the basis of the accessible literature examined in NAC patients, individuals who received the therapeutic regimen containing Atractylodis Macrocephalae Chinese herbal preparations demonstrated a superior overall response rate (Relative Risk: 1.41, 95% confidence interval: 1.27-1.57, P < 0.001); DCR (RR: 1.20, 95% confidence interval: 1.13-1.27, P < 0.001), as compared to QOL (RR: 1.43, 95% confidence interval: 1.30-1.57, P < 0.001, MD: 8.47, 95% confidence interval: 7.16 - 9.77, P < 0.001); the proportions of CD3+ T-cells, CD4+ T-cells, CD8+ T-cells, CD4+ CD8+ T-cells were increased; and the incidence of adverse reactions was decreased. Subgroup analyses showed that oral administration of all the traditional Chinese medicines containing Atractylodes macrocephala could improve tumor efficacy. Regardless of the duration of therapy of ≥8 weeks or <8 weeks, Atractylodes macrocephala-containing traditional Chinese medicine increased the tumor response in AGC patients. Combination of Atractylodes macrocephala-containing TCM with neoadjuvant chemotherapy increased ORR and DCR; when used in conjunction with cisplatin, only ORR was increased. Conclusion: The combination of Atractylodes macrocephala-containing herbs with NAC in the treatment of AGC improves efficacy, improves prognosis, and reduces adverse effects. Nevertheless, additional high-quality randomized trials are required. [ABSTRACT FROM AUTHOR]

BackgroundDepression is a prevalent comorbidity in patients with heart failure (HF). However, data regarding the prognostic significance of depression during the early post-discharge period in patients hospitalized with acute HF, regardless of left ventricular ejection fraction (LVEF), were scarce.Methods and resultsThe Heart Failure Registry of Patient Outcomes (HERO) study is a prospective, multicenter study of patients hospitalized with acute HF in China. At the first follow-up after discharge (median 4.0, interquartile range [IQR]: 2.4–6.1 weeks), depressive symptoms over the past 2 weeks were assessed using the Patient Health Questionnaire-9 (PHQ-9). Of 3,889 patients, 480 (12.3%) patients had depression (PHQ-9 score ≥ 10). A total of 3,456 patients (11.4% with depression) were included in the prospective analysis. After a median follow-up of 47.1 weeks (IQR: 43.9, 49.3) from the first follow-up, 508 (14.7%) patients died, and 1,479 (42.8%) patients experienced a composite event (death or HF rehospitalization). Cox proportional hazards models were used to assess the association of post-discharge depression with adverse events. After adjustment, post-discharge depression was associated with an increased risk of all-cause mortality (hazard ratio [HR] 2.38 [95% confidence interval (CI): 1.93–2.94]; p < 0.001) and the composite event (HR 1.78 [95% CI: 1.55–2.05]; p < 0.001). A per scale point increase in PHQ-9 score (ranging from 0 to 27 points) was associated with a 7.6% increase in all-cause mortality (HR 1.08 [95% CI: 1.06–1.09]; p < 0.001). In the subgroup analysis, the association between depression and the composite event was significantly stronger in relatively younger patients (< 75 vs. ≥ 75 years; p for interaction = 0.011), and the association between depression and all-cause mortality was significantly stronger in patients with preserved ejection fraction than in those with reduced ejection fraction (p for interaction = 0.036).ConclusionPost-discharge depression in patients recently hospitalized with acute HF is associated with an increased risk of adverse events, regardless of LVEF. Screening for depressive symptoms during the early post-discharge period may help to better identify high-risk patients and tailor patient management. Further studies are needed to determine how regular depression screening can help improve patient management and clinical outcomes.

COVID-19 caused by SARS-CoV-2 can cause various systemic diseases such as acute pneumonia with cytokine storm. Constituted of necroptosis, pyroptosis, and ferroptosis, regulated necrosis constitutes the cell death patterns under the low apoptosis condition commonly observed in COVID-19. Regulated necrosis is involved in the release of cytokines like TNF-α, IL-1 β, and IL-6 and cell contents such as alarmins, PAMPs, and DAMPs, leading to more severe inflammation. Uncontrolled regulated necrosis may explain the poor prognosis and cytokine storm observed in COVID-19. In this review, the pathophysiology and mechanism of regulated necrosis with the double-edged sword effect in COVID-19 are thoroughly discussed in detail. Furthermore, this review also focuses on the biomarkers and potential therapeutic targets of the regulated necrosis pathway in COVID-19, providing practical guidance to judge the severity, prognosis, and clinical treatment of COVID-19 and guiding the development of clinical anti-SARS-CoV-2 drugs.

China is the largest antimony resource globally. The mining and smelting of antimony will inevitably have a significant impact on the surrounding and downstream farmlands of the mining area, Therefore, it is necessary to understand the pollution characteristics of antimony and evaluate its potential environmental risks. In this paper, three typical antimony mining areas were used as research districts to analyze the contents of heavy metals in soils of the mining areas and watersheds. The single-factor pollution index method, Nemerow comprehensive pollution index method, geo-accumulation index method, and potential ecological risk index method were used to comprehensively evaluate the pollution status and ecological risk of heavy metals in soils around the mining areas. The soil around the Lengshuijiang tin mine was polluted by As, Cd, Zn, and Sb, it was a heavily polluted soil and at a high ecological risk level. The arable soil around the Nandan tea mountain antimony mine was polluted by As, Cd, Cu, Pb, Sb, and Zn, and it was a heavily polluted soil with very high ecological risk level. The soil around the Xunyang antimony mine was mainly polluted by Sb and it was a moderately polluted soil with moderate ecological risk level. The results revealed that the overall soil heavy metal levels in the Lengshuijiang mining area and the Nandan mining area were in a high-risk state, most likely due to the mining and smelting of metal ores and the weathering of mineralised rocks. showing a high-potential ecological risk in these mining areas. We expect to provide a scientific basis for the safe utilization of farmland and pollution control around the antimony mining areas and watersheds in China.

STEM education has been regarded as an important educational initiative for cultivating students' twenty-first century skills. The present work aimed to explore ways to promote students' twenty-first century skills through an integrated STEM-based curriculum. Specifically, we designed and implemented an 8-week crossover program of STEM and community service education. In this program, students learned about STEM domain knowledge and community service issues. They then applied the knowledge to solve authentic problems faced by Hong Kong community-housing residents from disadvantaged groups. A mixed-method approach was employed to evaluate the effectiveness of the program in enhancing students' twenty-first century skills and attitudes, including (i) creative thinking, (ii) collaboration, (iii) perseverance, as well as their (iv) STEM career interests. The research participants were 121 secondary students from a government-subsidized school. The quantitative results showed that the participants' creative thinking, collaboration, and perseverance improved alongside their STEM career interests. These findings were further supported by the data gathered through focus-group interviews. This study provides theoretical and practical insights into the integration of STEM education with community service learning.

Although the automatic speech recognition (ASR) technology is increasingly used for commercial purposes, its impact on language learning has not been extensively studied. Underpinned by the sociocultural theory, the present work examined the effects of leveraging ASR technology to support English vocabulary learning in a tertiary flipped setting. A control group and an experimental group of college students participated in a 14-week study. Both groups had their English classes in a flipped fashion, but the experimental group was assigned with ASR-assisted oral tasks for pre-class self-learning. The pre- and post-intervention in-class task performance of both groups was audio-recorded and transcribed for data analysis. The triadic complexity-accuracy-fluency (CAF) framework was adopted to evaluate the participants' vocabulary learning. The between- and within-subjects effects were examined mainly through procedures of MANCOVA and mixed-design repeated measures ANCOVA. Results showed that on all the metrics of lexical complexity and speed fluency, the experimental group outperformed the control group, and had significant growth over time. On the other hand, the control group only improved significantly overtime on the G-index. On lexical accuracy, there was no significant difference between the two groups, and the within-subjects effect was not significant for either group. The findings lent some support to Skehan's Trade-off Hypothesis and discussions were conducted regarding the triarchic CAF framework.

BackgroundAtrial fibrillation (AF) is associated with a high risk of mild cognitive impairment (MCI) and dementia. However, feasible and simple instruments that facilitate the regular assessment of cognitive status in patients with AF remain underdeveloped.MethodsCognitive function was first evaluated using telephone Montreal cognitive assessment (T-MoCA), and then patients were invited for an in-person interview for cognitive assessment using both Clinical Dementia Rating (CDR) and mini-mental status evaluation (MMSE). Using CDR = 0.5 as a reference standard, the ability of T-MoCA and MMSE to discriminate cognitive dysfunction, stratified by education level, was tested by receiver–operating curve (ROC) analysis. The net reclassification index was calculated for comparison between the performance of T-MoCA and MMSE.ResultsOne hundred and one patients completed both telephone and in-person interview. Thirty-five MCI patients were identified as MCI using the criteria of CDR = 0.5. The areas under the ROC curve of T-MoCA were 0.80 (0.71–0.89), 0.83 (0.71–0.95), and 0.85 (0.64–0.92) for all patients, patients with high educational level, and patients with low education level, respectively. The optimal threshold was achieved at 16/17 with a sensitivity of 85.7% and a specificity of 69.7% in overall patients, 15/16 with a sensitivity of 88.2% and a specificity of 64.5% in the low educational level patients, and 16/17 with a sensitivity of 77.8% and a specificity of 87.9% in the high educational level patients. Compared to the criterion MMSE ≤ 27 and MMSE norms for the elderly Chinese community, the stratified T-MoCA threshold improves correct classification by 23.7% (p = 0.033) and 30.3% (p = 0.020), respectively.ConclusionT-MoCA is a feasible and effective instrument for MCI screening in patients with AF.

BackgroundAnemia is common in patients with chronic heart failure (HF) and is associated with adverse outcomes. However, data regarding the prognostic value of on-admission anemia on mortality in patients hospitalized with acute HF were relatively limited and conflicting. This study aimed to investigate the association of on-admission anemia with 1-year mortality and evaluate whether anemia is an independent predictor of mortality in patients hospitalized with acute HF.MethodsThe present analysis included 4,244 patients hospitalized with acute HF from the HERO (Heart Failure Registry of Patient Outcomes) study. On-admission anemia was defined using the World Health Organization (WHO) criteria (hemoglobin

BackgroundTo build a predictive scoring model based on simple immune and inflammatory parameters to predict postoperative survival in patients with breast cancer.MethodsWe used a brand-new immuno-inflammatory index—pan-immune-inflammation value (PIV)—to retrospectively evaluate the relationship between PIV and overall survival (OS), and based on the results of Cox regression analysis, we established a simple scoring prediction model based on several independent prognostic parameters. The predictive accuracy of the model was evaluated and independently validated.ResultsA total of 1,312 patients were included for analysis. PIV was calculated as follows: neutrophil count (109/L) × platelet count (109/L) × monocyte count (109/L)/lymphocyte count (109/L). According to the best cutoff value of PIV, we divided the patients into two different subgroups, high PIV (PIV > 310.2) and low PIV (PIV ≤ 310.2), associated with significantly different survival outcomes (3-year OS, 80.26% vs. 86.29%, respectively; 5-year OS, 62.5% vs. 71.55%, respectively). Six independent prognostic factors were identified and used to build the scoring system, which performed well with a concordance index (C-index) of 0.759 (95% CI: 0.715–0.802); the calibration plot showed good calibration.ConclusionsWe have established and verified a simple scoring system for predicting prognosis, which can predict the survival of patients with operable breast cancer. This system can help clinicians implement targeted and individualized treatment strategies.

Background: Pancreatic adenocarcinoma (PDAC) is the most aggressive among all solid malignancies with delayed disease detection and limited effective treatment. However, due to the intricate heterogeneity and exclusive tumor microenvironment (TME), the development of effective therapy has been facing enormous challenges. The lysyl oxidases (LOXs) underpin the shaping of the TME to promote cancer growth, metastasis and modulate response to treatment.Materials and Methods: The mRNA expression, prognostic, and clinicopathological data for LOXs in PDAC from multiple open-access databases were summarized and analyzed. The protein expression was verified by immunohistochemistry (IHC). Co-expressed genes of LOXs were predicted and elaborated by LinkedOmics. Functional enrichment analysis of LOXs co-expressed genes was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). TIMER and TISIDB were applied to analyze the relationship between LOXs expression and immune infiltration.Results: The mRNA expression levels of LOX, LOXL1 and LOXL2 were significantly higher in PDAC, the expression levels of LOXL3 and LOXL4 were contrary in different databases. High mRNA levels of LOX and LOXL2 were associated with advanced PDAC stage, while elevated LOX and LOXL3 expression correlated with high tumor grade. The IHC staining showed higher expression levels of LOX, LOXL1 and LOXL2, lower expression level of LOXL3 in PDAC tissues, while the protein expression of LOXL4 made no difference. Functional enrichment analysis showed a close relationship with extracellular matrix (ECM) regulation, except that LOXL3 and its ligands were highly associated with immune-related functions. Further analysis suggested that LOX and LOXL3 strongly correlated with tumor-infiltrating lymphocytes (TILs), various immune signatures, and immune checkpoints. Finally, survival analysis revealed high LOX and LOXL2 expression predicted worse overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS).Conclusion: These findings indicated that the LOX family, especially LOX and LOXL2, might have a prospective value in PDAC oncogenesis, and they may become prognostic biomarkers, revealing a promising field in targeted therapy.

BackgroundThis study aimed to assess the clinical utility of the advanced lung cancer inflammation index (ALI) as a prognostic indicator for patients with cholangiocarcinoma (CCA) and construct a prognostic nomogram based on ALI.MethodsA total of 97 CCA patients who received radical resection were included. The optimal cut-off point for ALI was identified by X-tile analysis. COX regression analysis were used to identify risk factors of overall survival (OS) and disease-free survival (DFS). A predictive nomogram for DFS was constructed.ResultsThe optimal cut-off value for preoperative ALI was 31.8. 35 (36.1%) patients were categorized into the low-ALI group and 62 (63.9%) patients into the high-ALI group. Low ALI was independently associated with hypoproteinemia and lower body mass index (BMI) (all P < 0.05). COX regression analysis revealed that preoperative ALI level (HR = 0.974, P = 0.037) and pathological TNM stage (HR = 7.331, P < 0.001) were independently correlated with OS for patients with CCA, and preoperative ALI level (HR = 0.978, P = 0.042) and pathological T stage (HR = 1.473, P = 0.035) remained to be independent prognostic factors for DFS in CCA patients. Using time-dependent ROC analysis, we found that ALI was better at predicting prognosis than other parameters, such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI) in terms of OS and DFS. A nomogram predicting DFS was built (C-index: 0.73 95%CI: 0.67–0.79).ConclusionsALI may be useful for prognosis assessment for patients with CCA.

AimNeuroimaging studies have highlighted gender differences in brain functions, but conclusions are not well established. Few studies paid attention to the influence of phase-encoding (PE) direction in echo-planar imaging on gender differences, which is a commonly used technique in functional magnetic resonance imaging (fMRI). A disadvantage of echo-planar images is the geometrical distortion and signal loss due to large susceptibility effects along the PE direction. The present research aimed to clarify how PE direction can affect the outcome of a specific research on gender differences.MethodsWe collected resting-state fMRI using anterior to posterior (AP) and posterior to anterior (PA) directions from 113 healthy participants. We calculated several commonly used indices for spontaneous brain activity including amplitude of low frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC) of posterior cingulate cortex for each session, and performed three group comparisons: (i) AP versus PA; (ii) male versus female; (iii) interaction between gender and PE direction.ResultsThe estimated indices differed substantially between the two PE directions, and the regions that exhibited differences were roughly similar for all the indices. In addition, we found that multiple brain regions showed gender differences in these estimated indices. Further, we observed an interaction effect between gender and PE direction in the bilateral middle frontal gyrus, right precentral gyrus, right postcentral gyrus, right lingual gyrus, and bilateral cerebellum posterior lobe.ConclusionThese apparent findings revealed that PE direction can partially influence gender differences in spontaneous brain activity of resting-state fMRI. Therefore, future studies should document the adopted PE direction and appropriate selection of PE direction will be important in future resting-state fMRI studies.

Background: “Atrial fibrillation Better Care” (ABC) pathway has been proposed to improve the management of patients suffered from atrial fibrillation (AF). This integrated or holistic management approach comprise of three aspects, including “A” Avoid stroke or Anticoagulation; “B” Better symptom control with rate or rhythm control strategies; “C” Cardiovascular risk factor and Concomitant diseases management. We aimed to confirm the beneficial evidence of ABC pathway compliance in a Chinese AF cohort.Method and Results: From the Chinese Atrial Fibrillation registry (CAFR) dataset, a total of 19,187 non-valvular AF patients were enrolled, of which 4.365 (22.8%) were ABC pathway compliant (ABC compliance group). During a median follow-up of 4.1 ± 1.8 years, The incident rate of all-cause death in ABC compliance group and non-ABC compliance group is 2.7 and 1.1 per 100 person-year (p < 0.001), the incident rate of ischemic stroke is 1.3 and 0.8% per 100 person-year (p < 0.001), the incident rate of composite outcome, which consist of all-cause death, ischemic stroke and intracranial hemorrhage, is 3.8 and 1.9 per 100 person-year (p < 0.001). On Cox multivariable analysis, ABC pathway shows an independently association with reduction of all-cause death [hazard ratio (HR) = 0.82; 95% confidence interval (CI) = 0.70–0.95] and the composite outcome (HR 0.86, 95% CI 0.76–0.96). The increasingly components of ABC integrated care compliance is associated with lower risk of all-cause death and composite events.Conclusion: In a large cohort of Chinese AF patients, ABC pathway compliance shows an independently association with reduction of all-cause death and composite outcome of all-cause death, ischemic stroke and intracranial hemorrhage. Better compliance of ABC integrated care contributes to lower HR for adverse events.

The present study validated the general extended technology acceptance model for e-learning (GETAMEL) with the survey data from the English as a foreign language (EFL) online class during the novel coronavirus lockdown period. A total of 678 undergraduates participated in the survey. Structural equation modeling was employed to analyze the data. The results showed that the influence of perceived usefulness of students on their intentional behavior to use the online learning system was not mediated by their attitude, indicating a very limited role of attitude toward technology in the model. Enjoyment and self-efficacy had no significant effects on the internal constructs, raising theoretical concerns on the applicability of this general model into specific contexts. In addition, we found that experience might be a moderator rather than an antecedent of the internal constructs in the model.

Severe spinal cord injuries (SCIs) usually result in the temporary or permanent impairment of strength, sensation or autonomic functions below the sites of injuries. To date, a large number of therapeutic approaches have been used to ameliorate SCIs, and subsequent stem cell transplantation appears to be a promising strategy. The aim of this study was to evaluate the therapeutic effect of stem cells by changes in the evoked potentials at different time points after a transplantation of spermatogonial stem cells (SSCs) to differentiate the source neurons in a rat model with SCIs, as well as through histopathology. A modified Plemel spinal cord lateral compression model was used. The experiment was divided into a blank, a control and a SSC transplantation group. Motor activity scores, sensory evoked potentials (SEPs) and motor evoked potentials (MEPs) were assessed through motor resuscitation as well as histologic evaluation on each experimental group to determine the improvement. Consistent with our results, motor scores and evoked potentials were significantly improved in the SSC transplantation group. In addition, a histologic assessment showed that the transplanted stem cells had a significant restorative effect on the reconstruction of tissue cells. 1  week after the stem cell transplantation, the SSC transplantation group showed improvement in spinal cord functions and spinal cord pathologic injuries. After 2  weeks and beyond, the SSC transplantation group showed significant improvement in spinal cord functions and spinal cord pathology compared to the control group, meanwhile the evoked potentials and motor function of the hind limbs of rats in the SSC transplantation group were significantly improved. Therefore, the therapeutic strategies for spermatogonial stem cells will be an effective program in the study on SCIs, and we suggest the somatosensory evoked potentials as a tool to assess the degree of recovery from SCIs after the transplantation of stem cells. [ABSTRACT FROM AUTHOR]

The incidence of osteoporosis, which is primarily characterized by plethoric osteoclast (OC) formation and severe bone loss, has increased in recent years. Millions of people worldwide, especially postmenopausal women, suffer from osteoporosis. The drugs commonly used to treat osteoporosis still exist many disadvantages, but natural extracts provide options for the treatment of osteoporosis. Therefore, the identification of cost-effective natural compounds is important. Patchouli alcohol (PA), a natural compound extracted from Pogostemon cablin that exerts anti-inflammatory effects, is used as a treatment for gastroenteritis. However, no research on the use of Patchouli alcohol in osteoporosis has been reported. We found that PA dose-dependently inhibited the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced formation and function of OCs without cytotoxicity. Furthermore, these inhibitory effects were reflected in the significant effect of PA on the NF-κB signaling pathway, as PA suppressed the transcription factors NFATc1 and c-Fos. We also determined that PA activated expression of the nuclear receptor pregnane X receptor (PXR) and promoted the PXR/Toll-like receptor 4 (TLR4) axis to inhibit the nuclear import of NF-κB (p50 and p65). Additionally, PA exerted therapeutic effects against osteoporosis in ovariectomized (OVX) mice, supporting the use of PA as a treatment for osteoporosis in the future.

Osteoporosis, mainly caused by osteoclast-induced bone resorption, has become a major health problem in post-menopausal women and the elderly. Growing evidence indicates that inhibiting osteoclastogenesis is an efficient approach to develop alternative therapeutic agents for treating osteoporosis. In this study, we identified the potential regulating role of Oxymatrine (OMT), a quinazine alkaloid extracted from Sophora flavescens with various therapeutic effects in many diseases, on osteoclastogenesis for the first time. We found that OMT attenuated RANKL-induced osteoclast formation in both time- and dose-dependent manners. Further, OMT significantly suppressed RANKL-induced sterol regulatory element-binding protein 2 (SREBP2) activation and the expression of the nuclear factor of activated T cells 1 (NFATc1). Moreover, OMT inhibited the generation of RANKL-induced reactive oxygen species (ROS), and the upregulation of ROS could rescue the inhibition of SREBP2 by OMT. More importantly, ovariectomy (OVX) mouse model showed that OMT could effectively improve ovariectomy (OVX)-induced osteopenia by inhibiting osteoclastogenesis in vivo. In conclusion, our data demonstrated that OMT impaired ROS mediated SREBP2 activity and downstream NFATc1 expression during osteoclastogenesis, suppressed OVX-induced osteopenia in vivo, which suggested that OMT could be a promising compound for medical treatment against osteoporosis.

BackgroundThe combination of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) has shown significant clinical activity in patients with non-small cell lung cancer (NSCLC). However, the currently available data on adverse events (AEs) were derived from a small subset of patients included in prospective clinical trials or retrospective studies. Thus, we conducted this systematic review to determine the AEs associated with this combination treatment.MethodsAn electronic literature search was performed in databases and conference proceedings of prospective clinical trials assessing the combination of ICIs and TRT for patients with NSCLC. The systematic analysis was conducted to determine the profile and incidence of AEs of combination treatment. We further performed the comparison of AEs between programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, and sequential and concurrent administration of ICIs and TRT to help identify high risk patients. The systematic analyses were conducted with the Review Manager (version 5.3; The Cochrane Collaboration, Oxford, United Kingdom) and Stata version 12.0 (StataCorp, College Station, TX, USA) software.ResultsEleven clinical trials involving 1,113 patients with NSCLC were eligible for analysis. The incidence of all-grade AEs was 95.5%; that of high-grade AEs (grade ≥3) was 30.2%. The most frequent all-grade AE was fatigue (49.7%), while pneumonitis was the most common high-grade AE (3.8%) and grade 5 AE (0.6%). Notably, the toxicity profiles of PD-1 and PD-L1 inhibitors were similar. Concurrent treatment was associated with a higher incidence of higher-grade AEs (41.6% vs 24.8%, P=0.17) and pneumonitis (7.1% vs 3.9%, P=0.14) compared to sequential treatment, but no significant difference was observed.ConclusionMost AEs of this combination treatment are tolerable; as the most common high-grade AE, pneumonitis deserves the utmost attention of physicians. The toxicity profiles of patients receiving PD-1 or PD-L1 were similar, and no significant difference was observed between concurrent and sequential treatment.

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy and treatment failure is largely due to metastasis and invasion. Aberrant tumor cell adhesion is often associated with tumor progression and metastasis. However, the exact details of cell adhesion in ESCC progression have yet to be determined. In our study, the clinical relevance of Pax2 transactivation domain-interacting protein (PTIP/PAXIP1) was analyzed by immunohistochemistry of ESCC tissues. We found that low expression of PTIP was associated with lymph node metastasis in ESCC, and loss-of-function approaches showed that depletion of PTIP promoted ESCC cell migration and invasion both in vitro and in vivo. Analysis integrating RNA-seq and ChIP-seq data revealed that PTIP directly regulated ephrin type-A receptor 2 (EphA2) expression in ESCC cells. Moreover, PTIP inhibited EphA2 expression by competing with Fosl2, which attenuated the invasion ability of ESCC cells. These results collectively suggest that PTIP regulates ESCC invasion through modulation of EphA2 expression and hence presents a potential therapeutic target for its treatment.

Phenomenographic research about teachers’ conception of teaching has consistently revealed that teachers’ conception of teaching influence their classroom practices, which in turn shape students’ learning experiences. This paper reports teachers’ conceptions of teaching with regards to the use of interactive spherical video-based virtual reality (ISV-VR) in Chinese descriptive composition writing. Twenty-one secondary teachers in Hong Kong involved in an ISV-VR-supported Chinese descriptive writing program participated in this phenomenographic study. Analyses of the semi-structured interviews establish seven conception categories that are specifically related to the use of ISV-VR for descriptive Chinese composition writing: (1) offering students more observational opportunities; (2) improving students’ writing skills; (3) promoting students’ learning participation and motivation; (4) shifting learning from teacher-centric to student-centric, (5) enhancing collaborative learning among students; (6) cultivating students’ positive values and moral character, and (7) shaping students’ self-identity as “writers.” The concurrent and convenient access to the ISV-VR resources was for the teachers an enriched and supportive environment for them to cultivate students’ writer identity. In addition, it was discovered that the structural relationships of the conceptions may be better organized along three axes of continuum: conception’s orientation, teaching attention locus, and understanding of writing. These categories form a hierarchy from skill-oriented to community-oriented, and finally to identity-oriented conception. The findings may provide researchers and practitioners with novel insight into the teaching of composition writing in the contexts of L1 acquisition supported by virtual reality technology.

Previous studies have indicated that α1D/1A antagonist naftopidil (NAF) suppresses prostate growth by decreasing cell proliferation without affecting apoptosis and prostate volume in benign prostatic hyperplasia (BPH). A NAF-derived α1D/1A antagonist 1- benzyl-N-(3-(4-(2-methoxyphenyl) piperazine-1-yl) propyl)-1H-indole-2- carboxamide (HJZ-12) has been reported from our laboratory, which exhibits high subtype-selectivity to both α1D- and α1A- AR (47.9- and 19.1- fold, respectively) with respect to a1B-AR in vitro. However, no further study was conducted. In the present study, a pharmacological evaluation of HJZ-12 in BPH was performed on an estrogen/androgen-induced rat BPH model and human BPH-1 cell line. In vivo, HJZ-12 exhibited better performance than NAF in preventing the progression of rat prostatic hyperplasia by not only decreasing prostate weight and proliferation (similar to NAF) but also, shrinking prostate volume and inducing prostate apoptosis (different from NAF). In vitro, HJZ-12 exhibited significant cell viability inhibition and apoptotic induction in BPH-1 cell line, without presenting cell anti-proliferation properties. Intriguingly, the role of HJZ-12 on cell viability and apoptosis was an α1-independent action. Furthermore, RNA-Seq analysis was applied to screen out six anti-apoptotic genes (Bcl-3, B-lymphoma Mo-MLV insertion region 1 [Bmi-1], ITGA2, FGFR3, RRS1, and SGK1). Amongst them, Bmi-1 was involved in the apoptotic induction of HJZ-12 in BPH-1. Overall, HJZ-12 played a remarkable role in preventing the progression of prostatic hyperplasia through α1-independent apoptotic induction, indicating that it will be a multi-target effective candidate for BPH treatment.

In mammalian species, both the maturation promoting factor (MPF) and the mitogen-activated protein kinase (MAPK) cascade play critical roles in modulating oocyte meiotic cell-cycle progression. MPF is a critical heterodimer composed of CDK1 and cyclin B1. Activation of MPF and ERK1/2 requires the activation of maternal Ccnb1 and Mos mRNAs translation, respectively. The phosphorylation and degradation of CPEB1 that triggered by ERK1/2 is a principal mechanism of activating maternal mRNA translation. However, the interplay of these two key kinases in mediating mammalian translational activation of cytoplasmic mRNAs during oocyte maturation is unclear. We prove evidence that the translational activation of Ccnb1 transcripts containing a long 3′-UTR during meiotic resumption works in an ERK1/2-dependent way. A low level of ERK1/2 activation was detected prior to meiotic resumption. Precocious activation of MAPK signaling in germinal vesicle stage oocytes promotes the translation of Ccnb1 mRNA and meiotic maturation. Inhibition or precocious activation of CDK1 activity has an appreciable effect on the translation of Ccnb1 mRNA, suggesting that both kinases are required for Ccnb1 mRNA translational activation. CDK1 triggers phosphorylation, but not degradation, of CPEB1 in oocytes; the degradation of CPEB1 was only triggered by ERK1/2. Moreover, the translational activation of Mos mRNA is regulated by ERK1/2 and cytoplasmic polyadenylation elements too. Taken together, the cooperation and positive feedback activation of ERK1/2 and CDK1 lead to the fine-tuning of mRNA translation and cell-cycle progression during mouse oocyte maturation.

Spasticity is a major contributor to pain, disabilities and many secondary complications after stroke. Investigating the effect of spasticity on neuromuscular function in stroke patients may facilitate the development of its clinical treatment, while the underlying mechanism of spasticity still remains unclear. The aim of this study is to explore the difference in the neuromuscular response to passive stretch between healthy subjects and stroke patients with spasticity. Five healthy subjects and three stroke patients with spastic elbow flexor were recruited to complete the passive stretch at four angular velocities (10°/s, 60°/s, 120°/s, and 180°/s) performed by an isokinetic dynamometer. Meanwhile, the 64-channel electromyography (EMG) signals from biceps brachii muscle were recorded. The root mean square (RMS) and fuzzy entropy (FuzzyEn) of EMG recordings of each channel were calculated, and the relationship between the average value of RMS and FuzzyEn over 64-channel was examined. The two groups showed similar performance from results that RMS increased and FuzzyEn decreased with the increment of stretch velocity, and the RMS was negatively correlated with FuzzyEn. The difference is that stroke patients showed higher RMS and lower FuzzyEn during quick stretch than the healthy group. Furthermore, compared with the healthy group, distinct variations of spatial distribution within the spastic muscle were found in the EMG activity of stroke patients. These results suggested that a large number of motor units were recruited synchronously in the presence of spasticity, and this recruitment pattern was non-uniform in the whole muscle. Using a combination of RMS and FuzzyEn calculated from high-density EMG (HD-EMG) recordings can provide an innovative insight into the physiological mechanism underlying spasticity, and FuzzyEn could potentially be used as a new indicator for spasticity, which would be beneficial to clinical intervention and further research on spasticity.

Plant viruses may serve as expression vectors for the efficient production of pharmaceutical proteins in plants. However, the downstream processing and post-translational modifications of the target proteins remain the major challenges. We have previously developed an expression system derived from Bamboo mosaic virus (BaMV), designated pKB19, and demonstrated its applicability for the production of human mature interferon gamma (mIFNγ) in Nicotiana benthamiana. In this study, we aimed to enhance the yields of soluble and secreted mIFNγ through the incorporation of various plant-derived signal peptides. Furthermore, we analyzed the glycosylation patterns and the biological activity of the mIFNγ expressed by the improved pKB19 expression system in N. benthamiana. The results revealed that the fusion of a native N. benthamiana extensin secretory signal (SSExt) to the N-terminal of mIFNγ (designated SSExt mIFNγ) led to the highest accumulation level of protein in intracellular (IC) or apoplast washing fluid (AWF) fractions of N. benthamiana leaf tissues. The addition of 10 units of ‘Ser-Pro’ motifs of hydroxyproline-O-glycosylated peptides (HypGPs) at the C-terminal end of SSExt mIFNγ (designated SSExt mIFNγ(SP)10) increased the solubility to nearly 2.7- and 1.5-fold higher than those of mIFNγ and SSExt mIFNγ, respectively. The purified soluble SSExt mIFNγ(SP)10 protein was glycosylated with abundant complex-type N-glycan attached to residues N56 and N128, and exhibited biological activity against Sindbis virus and Influenza virus replication in human cell culture systems. In addition, suspension cell cultures were established from transgenic N. benthamiana, which produced secreted SSExt mIFNγ(SP)10 protein feasible for downstream processing. These results demonstrate the applicability of the BaMV-based vector systems as a useful alternative for the production of therapeutic proteins, through the incorporation of appropriate fusion tags.