Identification of ASF1A and HJURP by global H3-H4 histone chaperone analysis as a prognostic two-gene model in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignancy with poor prognosis. Abnormal expression of H3-H4 histone chaperones has been identified in many cancers and holds promise as a biomarker for diagnosis and prognosis. However, systemic analysis of H3-H4 histone chaperones in HCC is still lacking. Here, we investigated the expression of 19 known H3-H4 histone chaperones in HCC. Integrated analysis of multiple public databases indicated that these chaperones are highly expressed in HCC tumor tissues, which was further verified by immunohistochemistry (IHC) staining in offline samples. Additionally, survival analysis suggested that HCC patients with upregulated H3-H4 histone chaperones have poor prognosis. Using LASSO and Cox regression, we constructed a two-gene model (ASF1A, HJURP) that accurately predicts prognosis in ICGC-LIRI and GEO HCC data, which was further validated in HCC tissue microarrays with follow-up information. GSEA revealed that HCCs in the high-risk group were associated with enhanced cell cycle progression and DNA replication. Intriguingly, HCCs in the high-risk group exhibited increased immune infiltration and sensitivity to immune checkpoint therapy (ICT). In summary, H3-H4 histone chaperones play a critical role in HCC progression, and the two-gene (ASF1A, HJURP) risk model is effective for predicting survival outcomes and sensitivity to immunotherapy for HCC patients.

Exploring deep learning radiomics for classifying osteoporotic vertebral fractures in X-ray images.

Purpose: To develop and validate a deep learning radiomics (DLR) model that uses X-ray images to predict the classification of osteoporotic vertebral fractures (OVFs). Material and methods: The study encompassed a cohort of 942 patients, involving examinations of 1076 vertebrae through X-ray, CT, and MRI across three distinct hospitals. The OVFs were categorized as class 0, 1, or 2 based on the Assessment System of Thoracolumbar Osteoporotic Fracture. The dataset was divided randomly into four distinct subsets: a training set comprising 712 samples, an internal validation set with 178 samples, an external validation set containing 111 samples, and a prospective validation set consisting of 75 samples. The ResNet-50 architectural model was used to implement deep transfer learning (DTL), undergoing -pre-training separately on the RadImageNet and ImageNet datasets. Features from DTL and radiomics were extracted and integrated using X-ray images. The optimal fusion feature model was identified through least absolute shrinkage and selection operator logistic regression. Evaluation of the predictive capabilities for OVFs classification involved eight machine learning models, assessed through receiver operating characteristic curves employing the "One-vs-Rest" strategy. The Delong test was applied to compare the predictive performance of the superior RadImageNet model against the ImageNet model. Results: Following pre-training separately on RadImageNet and ImageNet datasets, feature selection and fusion yielded 17 and 12 fusion features, respectively. Logistic regression emerged as the optimal machine learning algorithm for both DLR models. Across the training set, internal validation set, external validation set, and prospective validation set, the macro-average Area Under the Curve (AUC) based on the RadImageNet dataset surpassed those based on the ImageNet dataset, with statistically significant differences observed (P<0.05). Utilizing the binary "One-vs-Rest" strategy, the model based on the RadImageNet dataset demonstrated superior efficacy in predicting Class 0, achieving an AUC of 0.969 and accuracy of 0.863. Predicting Class 1 yielded an AUC of 0.945 and accuracy of 0.875, while for Class 2, the AUC and accuracy were 0.809 and 0.692, respectively. Conclusion: The DLR model, based on the RadImageNet dataset, outperformed the ImageNet model in predicting the classification of OVFs, with generalizability confirmed in the prospective validation set.

Single-cell transcriptomics reveals ferrimagnetic vortex iron oxide nanoring-mediated mild magnetic hyperthermia exerts antitumor effects by alleviating macrophage suppression in breast cancer.

The potential of Ferrimagnetic vortex iron oxide nanoring-mediated mild magnetic hyperthermia (FVIO-MHT) in solid tumor therapy has been demonstrated. However, the impact of FVIO-MHT on the tumor microenvironment (TME) remains unclear. This study utilized single-cell transcriptome sequencing to examine the alterations in the TME in response to FVIO-MHT in breast cancer. The results revealed the cellular composition within the tumor microenvironment (TME) was primarily modified due to a decrease in tumor cells and an increased infiltration of myeloid cells. Subsequently, an enhancement in active oxygen (ROS) metabolism was observed, indicating oxidative damage to tumor cells. Interestingly, FVIO-MHT reprogrammed the macrophages' phenotypes, as evidenced by alterations in the transcriptome characteristics associated with both classic and alternative activated phenotypes. And an elevated level of ROS generation and oxidative phosphorylation suggested that activated phagocytosis and inflammation occurred in macrophages. Additionally, cell-cell communication analysis revealed that FVIO-MHT attenuated the suppression between tumor cells and macrophages by inhibiting phagocytic checkpoint and macrophage migration inhibitory factor signaling pathways. Inhibition of B2m, an anti-phagocytosis checkpoint, could promote macrophage-mediated phagocytosis and significantly inhibit tumor growth. These data emphasize FVIO-MHT may promote the antitumor capabilities of macrophages by alleviating the suppression between tumor cells and macrophages.

The association between jaundice and poorly differentiated pancreatic neuroendocrine neoplasms (Ki67 index > 55.0%).

BACKGROUND: Jaundice occurs in some pancreatic disease. However, its occurrences and role in pancreatic neuroendocrine neoplasms (PNENs) has not been well studied. In this study we showed the association between jaundice and the risk of high grade and poorly differentiated PNENs. METHODS: Ninety-three patients with head-neck PNENs were included. Poorly differentiated pancreatic neuroendocrine neoplasms were defined by a ki67 index > 55.0%. Logistic regression was used to show the association between demographic information, clinical signs and symptoms and the risk of poorly differentiated tumors. A nomogram model was developed to predict poorly differentiated tumor. RESULTS: Eight of 93 PNEN patients (8.6%) had jaundice. The age and ki67 index in patients with jaundice were significantly higher than those patients without jaundice. All jaundice occurred in patients with grade 3 PNENs. Mutivariable regression analysis showed that age (odds ratio(OR) = 1.10, 95% confidence interval (CI):1.02-1.19), tumor size (OR = 1.42, 95%CI:1.01-2.00) and jaundice (OR = 14.98, 95%CI: 1.22-184.09) were associated with the risk of poorly differentiated PNENs. The age and size combination showed a good performance in predicting poorly differentiated PNENs (area under the curve (AUC) = 0.81, 95% CI: 0.71-0.90). The addition of jaundice further improved the age- and size-based model (AUC = 0.86, 95% CI: 0.78-0.91). A nomogram was developed based on age, tumor size and jaundice. CONCLUSION: Our data showed that jaundice was associated with the risk of high grade PNENs and poorly differentiated PNENs.

Enhancing Mechanical Properties: Exploring the Effect of Annealing Temperature on Wire Arc Additively Manufactured High-Strength Steel.

This study investigates the mechanical properties of exceptionally high-strength steel produced by wire and arc additive manufacturing (WAAM), using the 304 stainless steel wire and the low carbon wire (LCS). The study found that annealing treatment can enhance the steel's mechanical properties. The microstructure in the LCS layer changed from ferrite to bainite and then to a mixture of austenite, pearlite, and bainite with increasing annealing temperature. In contrast, the SS layer retained its martensitic structure, albeit with altered lath sizes. The annealing treatment also improved the orientation of the grains in the steel. The optimal annealing temperature observed for the steel was 900 ℃, which resulted in a maximum tensile strength of 1176 MPa along the Y direction and 1255 MPa along the Z direction. Despite the superior mechanical properties, the LCS layer still exhibited failure during tensile testing due to its lower hardness. The study suggests that annealing treatment can be a useful technique for enhancing the mechanical properties of high-strength steel in WAAM applications.

Constructing a Deep Learning Radiomics Model Based on X-ray Images and Clinical Data for Predicting and Distinguishing Acute and Chronic Osteoporotic Vertebral Fractures: A Multicenter Study.

RATIONALE AND OBJECTIVES: To construct and validate a deep learning radiomics (DLR) model based on X-ray images for predicting and distinguishing acute and chronic osteoporotic vertebral fractures (OVFs). METHODS: A total of 942 cases (1076 vertebral bodies) with both vertebral X-ray examination and MRI scans were included in this study from three hospitals. They were divided into a training cohort (n = 712), an internal validation cohort (n = 178), an external validation cohort (n = 111), and a prospective validation cohort (n = 75). The ResNet-50 model architecture was used for deep transfer learning (DTL), with pre-training performed on RadImageNet and ImageNet datasets. DTL features and radiomics features were extracted from lateral X-ray images of OVFs patients and fused together. A logistic regression model with the least absolute shrinkage and selection operator was established, with MRI showing bone marrow edema as the gold standard for acute OVFs. The performance of the model was evaluated using receiver operating characteristic curves. Eight machine learning classification models were evaluated for their ability to distinguish between acute and chronic OVFs. The Nomogram was constructed by combining clinical baseline data to achieve visualized classification assessment. The predictive performance of the best RadImageNet model and ImageNet model was compared using the Delong test. The clinical value of the Nomogram was evaluated using decision curve analysis (DCA). RESULTS: Pre-training resulted in 34 and 39 fused features after feature selection and fusion. The most effective machine learning algorithm in both DLR models was Light Gradient Boosting Machine. Using the Delong test, the area under the curve (AUC) for distinguishing between acute and chronic OVFs in the training cohort was 0.979 and 0.972 for the RadImageNet and ImageNet models, respectively, with no statistically significant difference between them (P = 0.235). In the internal validation cohort, external validation cohort, and prospective validation cohort, the AUCs for the two models were 0.967 vs 0.629, 0.886 vs 0.817, and 0.933 vs 0.661, respectively, with statistically significant differences in all comparisons (P < 0.05). The deep learning radiomics nomogram (DLRN) was constructed by combining the predictive model of RadImageNet with clinical baseline features, resulting in AUCs of 0.981, 0.974, 0.895, and 0.902 in the training cohort, internal validation cohort, external validation cohort, and prospective validation cohort, respectively. Using the Delong test, the AUCs for the fused feature model and the DLRN in the training cohort were 0.979 and 0.981, respectively, with no statistically significant difference between them (P = 0.169). In the internal validation cohort, external validation cohort, and prospective validation cohort, the AUCs for the two models were 0.967 vs 0.974, 0.886 vs 0.895, and 0.933 vs 0.902, respectively, with statistically significant differences in all comparisons (P < 0.05). The Nomogram showed a slight improvement in predictive performance in the internal and external validation cohort, but a slight decrease in the prospective validation cohort (0.933 vs 0.902). DCA showed that the Nomogram provided more benefits to patients compared to the DLR models. CONCLUSION: Compared to the ImageNet model, the RadImageNet model has higher diagnostic value in distinguishing between acute and chronic OVFs. Furthermore, the diagnostic performance of the model is further improved when combined with clinical baseline features to construct the Nomogram.

Association of Plasma Lipids with White Matter Hyperintensities in Patients with Acute Ischemic Stroke.

Purpose: White matter hyperintensities (WMH) are the common marker of cerebral small vessel disease (CSVD). Dyslipidemia plays a notable role in the pathogenesis of CSVD. However, the relationship between dyslipidemia and WMH is poorly elucidated. This study aims to investigate the association between serum lipid fractions and WMH in patients with acute ischemic stroke (AIS). Patients and Methods: A total of 901 patients with AIS were included in this study. The burden of WMH, including deep white matter hyperintensities (DWMH), periventricular white matter hyperintensities (PVWMH), and total WMH load, were evaluated on magnetic resonance imaging (MRI) by the Fazekas scale. All the WMH burden were set as dichotomous variables. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) were collected. The association of serum lipid fractions with WMH burden was analyzed using univariate and multivariate logistic regression models. Results: The average age of the participants was 67.6±11.6 years, and 584 cases (64.8%) were male. About 33.5% (n = 302) patients were smoker, and 23.5% (n = 212) patients had a history of alcohol consumption. The proportion of previous diabetes, ischemic cardiomyopathy and hypertension was 39.0% (n = 351), 21.2% (n = 191) and 75.9% (n = 684), respectively. The average of serum HDL-c, TC, TG, LDL-c levels for all participants were 1.26 ± 0.28 mmol/l, 4.54 ± 1.06 mmol/l, 1.67 ± 1.09 mmol/l, 3.08 ± 0.94 mmol/l. There were no statistical associations between HDL-c, TG, TC, LDL-c and each type of WMH burden (P > 0.05) in multivariate logistic regression analysis. Similar findings were found in subgroup analysis based on gender classification. Conclusion: Serum lipid levels were not associated with the presence of any type of WMH in patients with AIS.

Application of real time shear wave elastography to the differential diagnosis of secondary parathyroid hyperplasia and adenoma.

We aimed to explore the value of ultrasonic elastic imaging in the diagnosis of parathyroid hyperplasia and adenoma in patients with secondary hyperparathyroidism and provide more evidence for clinical treatment. Forty patients who were on dialysis and underwent parathyroid surgery were selected All patients underwent routine ultrasound, ultrasound elasticity examination and blood biochemical examination before surgery, including calcium, phosphorus, parathyroid hormone (PTH), etc. According to postoperative results, adenoma group and hyperplasia group were divided into 2 groups. Receiver operating characteristic curve was drawn to evaluate the diagnostic efficacy and combined diagnostic efficacy of each index. The PTH levels significantly differed between the adenoma and hyperplasia groups (P < .001). The volume and blood flow grades significantly differed between the adenoma and hyperplasia groups (P < .001) The minimum of the adenoma group was 14.62 ±â€…6.79 kPa, mean was 19.42 ±â€…6.29 kPa, and maximum was 24.25 ±â€…6.35 kPa which were significantly different from those in the hyperplasia group (P < .05). The combinations of more than 6 indicators in the diagnosis of parathyroid adenoma resulted in an area under the curve of 0.892 (P < .001), and the sensitivity and specificity were 78.9% and 97.4%, respectively. Shear wave elastography can be used as an effective tool to distinguish secondary parathyroid hyperplasia from adenoma. When combined with PTH, conventional ultrasound blood flow grading and volume measurement, it has higher diagnostic efficacy.

Testbed as a RegUlatory Science Tool (TRUST): A Testbed Design for Evaluating 5G-Enabled Medical Devices.

The fifth-generation (5G) cellular communication technology introduces technical advances that can expand medical device access to connectivity services. However, assessing the safety and effectiveness of emerging 5G-enabled medical devices is challenging as relevant evaluation methods have not yet been established. In this paper, we propose a design model for 5G testbed as a regulatory science tool (TRUST) for assessing 5G connectivity enablers of medical device functions. Specifically, we first identify application specific testing needs and general testing protocols. Next, we outline the selection and customization of key system components to create a 5G testbed. A TRUST demonstration is documented through a realistic 5G testbed implementation along with the deployment of a custom-built example use-case for 5G-enabled medical extended reality (MXR). Detailed configurations, example collected data, and implementation challenges are presented. The openness of the TRUST design model allows a TRUST testbed to be easily extended and customized to incorporate available resources and address the evaluation needs of different stakeholders.

Roles of GFAT and PFK genes in energy metabolism of brown planthopper, Nilaparvata lugens.

Glutamine:fructose-6-phosphate aminotransferases (GFATs) and phosphofructokinase (PFKs) are the principal rate-limiting enzymes involved in hexosamine biosynthesis pathway (HBP) and glycolysis pathway, respectively. In this study, the NlGFAT and NlPFK were knocked down through RNA interference (RNAi) in Nilaparvata lugens, the notorious brown planthopper (BPH), and the changes in energy metabolism were determined. Knockdown of either NlGFAT or NlPFK substantially reduced gene expression related to trehalose, glucose, and glycogen metabolism pathways. Moreover, trehalose content rose significantly at 72 h after dsGFAT injection, and glycogen content increased significantly at 48 h after injection. Glucose content remained unchanged throughout the experiment. Conversely, dsPFK injection did not significantly alter trehalose, but caused an extreme increase in glucose and glycogen content at 72 h after injection. The Knockdown of NlGFAT or NlPFK significantly downregulated the genes in the glycolytic pathway, as well as caused a considerable and significant decrease in pyruvate kinase (PK) activity after 48 h and 72 h of inhibition. After dsGFAT injection, most of genes in TCA cycle pathway were upregulated, but after dsNlPFK injection, they were downregulated. Correspondingly, ATP content substantially increased at 48 h after NlGFAT knockdown but decreased to an extreme extent by 72 h. In contrast, ATP content decreased significantly after NlPFK was knocked down and returned. The results have suggested the knockdown of either NlGFAT or NlPFK resulted in metabolism disorders in BPHs, highlighting the difference in the impact of those two enzyme genes on energy metabolism. Given their influence on BPHs energy metabolism, developing enzyme inhibitors or activators may provide a biological control for BPHs.

Congenital absence of the left pericardium: a case report.

BACKGROUND: Congenital absence of the pericardium (CAP) is rare in clinical practice, the symptoms vary among patients, and most doctors do not have enough knowledge of the condition. Most reported CAP cases are incidental findings. Therefore, this case report aimed to present a rare case of left partial CAP that presented with non-specific, possibly cardiac-related symptoms. CASE PRESENTATION: The patient, male, 56 years old, Asian, was admitted on March 2, 2021. The patient complained of occasional dizziness in the past week. The patient was suffering from hyperlipidemia and hypertension (stage 2), both untreated. The patient reported chest pain, palpitations, discomfort in the precordium, and dyspnea in the lateral recumbent position after strenuous activities, all of which started when he was about 15 years old. ECG showed sinus rhythm, 76 bpm, premature ventricular beats, incomplete right bundle branch block, and clockwise rotation of the electrical axis. Most of the ascending aorta could be detected in the parasternal intercostal space 2-4 by transthoracic echocardiography in the left lateral position. Chest computed tomography revealed the absence of pericardium between the aorta and the pulmonary artery, and part of the left lung was extending into the space. No changes in his condition have been reported up to now (March 2023). CONCLUSIONS: CAP should be considered when multiple examinations suggest heart rotation and a large moving range of the heart in the thoracic cavity.

Dynamic changes of resting state functional network following acute ischemic stroke.

Stroke, the second common cause of death in the world, is commonly considered to the well-known phenomenon of diaschisis. After stroke, regions far from the lesion can show altered neural activity. However, the comprehensive treatment recovery mechanism of acute ischemic stroke remains unclear. This study aims to investigate the impact of comprehensive treatment on resting state brain functional connectivity to reveal the therapeutic mechanism through a three time points study design. Twenty-one acute ischemic stroke patients and twenty matched healthy controls (HC) were included. Resting state functional magnetic resonance imaging (fMRI) and clinical evaluations were assessed in three stages: baseline (less than 72 h after stroke onset), post-first month and post-third month. Amplitude of low-frequency fluctuations (ALFF) and Independent component analysis (ICA) were conducted. We found: 1) stroke patients had decreased ALFF in the right cuneus (one of the important parts of the visual network). After three months, ALFF increased to the normal level; 2) the decreased functional connectivity in the right cuneus within the visual network and restored three months after onset. However, the decreased functional connectivity in the right precuneus within the default mode network restored one month after onset; 3) a significant association was found between the clinical scale score change over time and improvement in the cuneus and precuneus functional connectivity. Our results demonstrate the importance of the cuneus and precuneus within the visual network and default mode network in stroke recovery. These findings suggest that the different restored patterns of neural functional networks may contribute to the neurological function recovery. It has potential applications from stroke onset through rehabilitation because different rehabilitation phase corresponds to specific strategies.

Effect of direct endovascular treatment versus standard bridging therapy in large artery anterior circulation stroke (DEVT): 18-month follow-up of a randomized controlled trial.

BACKGROUND: Two trials in Chinese population showed that endovascular treatment (EVT) alone was noninferior to alteplase follow by EVT at 90 days. However, results of long-term clinical outcomes remain unknown. We reported the results of prespecified 18-month analysis of the DEVT trail. MATERIALS AND METHODS: We assessed clinical outcomes 18 months after patients were randomly assigned to receive EVT alone or bridging therapy for acute ischemic stroke (AIS). The primary outcome was the proportion of functional independence [modified Rankin scale (mRS), 0-2] at 18 months. Secondary outcomes included all-cause mortality and the quality of life at 18 months as measured by means of a health utility index according to the European Quality of Life 5-Dimension 5-level scale (EQ-5D-5L). Kaplan-Meier event curves were used to investigate the risk of mortality in participants with EVT alone or bridging therapy. RESULTS: Among 234 patients (EVT alone, n = 116; bridging therapy, n = 118) in the DEVT trial, only 231 (98.7%) patients were extended follow-up to 18 months. A total of 60 (51.7%) patients in the EVT alone achieved functional independence vs 56 (47.5%) patients in the bridging therapy (difference, 4.3%; 1-sided 97.5% CI, - 8.4% to ∞, P for noninferiority =0.014). No significant between-group difference was detected in EQ-5D-5L score (0.81 vs 0.73; difference, 0; 95% CI, 0 to 0.005). The cumulative mortality was 27.6% in the EVT alone and 28.8% in the bridging therapy. CONCLUSION: At 18 months follow-up, EVT alone was noninferior to bridging therapy regarding favorable functional outcome in patients with AIS. TRIAL REGISTRATION: Trial was registered on Chinese Clinical Trial Registry (ChiCTR-IOR-17013568) on 27/11/2017.

Research progress of hydrogels as delivery systems and scaffolds in the treatment of secondary spinal cord injury.

Secondary spinal cord injury (SSCI) is the second stage of spinal cord injury (SCI) and involves vasculature derangement, immune response, inflammatory response, and glial scar formation. Bioactive additives, such as drugs and cells, have been widely used to inhibit the progression of secondary spinal cord injury. However, the delivery and long-term retention of these additives remain a problem to be solved. In recent years, hydrogels have attracted much attention as a popular delivery system for loading cells and drugs for secondary spinal cord injury therapy. After implantation into the site of spinal cord injury, hydrogels can deliver bioactive additives in situ and induce the unidirectional growth of nerve cells as scaffolds. In addition, physical and chemical methods can endow hydrogels with new functions. In this review, we summarize the current state of various hydrogel delivery systems for secondary spinal cord injury treatment. Moreover, functional modifications of these hydrogels for better therapeutic effects are also discussed to provide a comprehensive insight into the application of hydrogels in the treatment of secondary spinal cord injury.

Development and validation of a novel ferroptosis­related lncRNA prognostic signature for pancreatic adenocarcinoma.

Long non­coding RNAs (lncRNAs) serve a pivotal role in the regulation of cancer cell ferroptosis. However, the prognostic value of ferroptosis­related lncRNAs in pancreatic adenocarcinoma (PAAD) largely remains unclear. We aimed at constructing a lncRNA­based signature to improve the prognosis prediction of PAAD. In the present study, the transcriptome profiling data and clinical information of patients with PAAD were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Gene Consortium (ICGC) databases. Univariate Cox regression analysis of the TCGA cohort demonstrated that 26 ferroptosis­related lncRNAs had significant prognostic value for PAAD (all P<0.01). Least absolute shrinkage and selection operator regression and multivariate Cox proportional hazards regression analyses were performed to construct a prognostic ferroptosis­related lncRNA signature (FRLS) comprising nine ferroptosis­related lncRNAs. The efficacy of this FRLS was verified in the training (TCGA) and validation (ICGC) cohorts. Based on the risk model, high risk scores were significantly correlated with poor overall survival (OS) (hazard ratio, 1.314; 95% confidence interval, 1.218­1.418; P<0.001). The receiver operating characteristic curves and principal component analysis further demonstrated the robust prognostic ability of the FRLS. Furthermore, a nomogram with favorable predictive efficacy for the prediction of OS was constructed based on the FRLS and clinical features. Gene set enrichment analysis demonstrated that the genes in the FRLS participated in a number of cancer­associated immunoregulatory pathways. Importantly, it was demonstrated that immune infiltration and response to cancer immunotherapy differed significantly between the high and low­risk groups according to the FRLS. In conclusion, the risk signature based on the FRLS has potential for the clinical prediction of prognosis and immunotherapy response in patients with PAAD.

Acupuncture-Neuroimaging Research Trends over Past Two Decades: A Bibliometric Analysis.

OBJECTIVE: To identify topics attracting growing research attention as well as frontier trends of acupuncture-neuroimaging research over the past two decades. METHODS: This paper reviewed data in the published literature on acupuncture neuroimaging from 2000 to 2020, which was retrieved from the Web of Science database. CiteSpace was used to analyze the publication years, countries, institutions, authors, keywords, co-citation of authors, journals, and references. RESULTS: A total of 981 publications were included in the final review. The number of publications has increased in the recent 20 years accompanied by some fluctuations. Notably, the most productive country was China, while Harvard University ranked first among institutions in this field. The most productive author was Tian J with the highest number of articles (50), whereas the most co-cited author was Hui KKS (325). Evidence-Based Complementary and Alternative Medicine (92) was the most prolific journal, while Neuroimage was the most co-cited journal (538). An article written by Hui KKS (2005) exhibited the highest co-citation number (112). The keywords "acupuncture" (475) and "electroacupuncture" (0.10) had the highest frequency and centrality, respectively. Functional magnetic resonance imaging (fMRI) ranked first with the highest citation burst (6.76). CONCLUSION: The most active research topics in the field of acupuncture-neuroimaging over the past two decades included research type, acupoint specificity, neuroimaging methods, brain regions, acupuncture modality, acupoint specificity, diseases and symptoms treated, and research type. Whilst research frontier topics were "nerve regeneration", "functional connectivity", "neural regeneration", "brain network", "fMRI" and "manual acupuncture".

Application of stimuli-responsive nanomedicines for the treatment of ischemic stroke.

Ischemic stroke (IS) refers to local brain tissue necrosis which is caused by impaired blood supply to the carotid artery or vertebrobasilar artery system. As the second leading cause of death in the world, IS has a high incidence and brings a heavy economic burden to all countries and regions because of its high disability rate. In order to effectively treat IS, a large number of drugs have been designed and developed. However, most drugs with good therapeutic effects confirmed in preclinical experiments have not been successfully applied to clinical treatment due to the low accumulation efficiency of drugs in IS areas after systematic administration. As an emerging strategy for the treatment of IS, stimuli-responsive nanomedicines have made great progress by precisely delivering drugs to the local site of IS. By response to the specific signals, stimuli-responsive nanomedicines change their particle size, shape, surface charge or structural integrity, which enables the enhanced drug delivery and controlled drug release within the IS tissue. This breakthrough approach not only enhances therapeutic efficiency but also mitigates the side effects commonly associated with thrombolytic and neuroprotective drugs. This review aims to comprehensively summarize the recent progress of stimuli-responsive nanomedicines for the treatment of IS. Furthermore, prospect is provided to look forward for the better development of this field.

N6-methyladenosine modification governs liver glycogenesis by stabilizing the glycogen synthase 2 mRNA.

Hepatic glycogen is the main source of blood glucose and controls the intervals between meals in mammals. Hepatic glycogen storage in mammalian pups is insufficient compared to their adult counterparts; however, the detailed molecular mechanism is poorly understood. Here, we show that, similar to glycogen storage pattern, N6-methyladenosine (m6A) modification in mRNAs gradually increases during the growth of mice in liver. Strikingly, in the hepatocyte-specific Mettl3 knockout mice, loss of m6A modification disrupts liver glycogen storage. On the mechanism, mRNA of Gys2, the liver-specific glycogen synthase, is a substrate of METTL3 and plays a critical role in m6A-mediated glycogenesis. Furthermore, IGF2BP2, a "reader" protein of m6A, stabilizes the mRNA of Gys2. More importantly, reconstitution of GYS2 almost rescues liver glycogenesis in Mettl3-cKO mice. Collectively, a METTL3-IGF2BP2-GYS2 axis, in which METTL3 and IGF2BP2 regulate glycogenesis as "writer" and "reader" proteins respectively, is essential on maintenance of liver glycogenesis in mammals.

The associations between serum high-density lipoprotein cholesterol levels and malignant behavior in pancreatic neuroendocrine neoplasms.

BACKGROUND: The role of serum high-density lipoprotein cholesterol (HDL-c) in tumorigenesis are observed in several endocrine-related cancers. However, its role in pancreatic neuroendocrine neoplasms (PNENs) has not been understood. In the current study, the relationship between HDL-c levels and malignant behavior in PNENs was explored. METHODS: One hundred ninety-seven patients with histopathology confirmed PNENs were included. PNENs were divided into three grades (G1, G2 and G3) as 2017 WHO classification based on ki67 index and mitosis count. The demographic data, clinical information, tumor morphological and pathological features (organs invasion, lymph node metastasis, vascular invasion and perineural invasion), and serum tumor biomarkers were collected. The relationships between HDL-c levels and malignant behaviors in PNENs were analyzed using logistic regression analysis. Models were also developed for the identification of high grade PNENs. RESULTS: The levels of serum HDL-c in G2/G3 tumor were significantly lower than that in G1 tumor (P = 0.031). However, no such difference was found between G3 and G1/G2. The proportions of low HDL-c (≤ 0.9 mmol/L) were higher in high-grade PNENs (G2/G3 or G3) than those in low-grade (G1 or G1/G2) (29.0 vs 15.2%, P = 0.032; 37.0 vs 20.5%, P = 0.023). The risk of G2/G3 tumors in patients with high serum HDL-c levels was decreased (odds ratio (OR) = 0.35, 95% confidence interval (CI): 0.12-0.99). Similarly, the risk of G3 PNENs increased in patients with low HDL-c levels (OR = 2.51, 95%CI:1.12-5.60). HDL-c level was also associated with a high ki67 index (> 55%) (OR = 0.10, 95%CI: 0.02-0.51) and neuroendocrine carcinoma G3 (OR = 0.21, 95%CI: 0.06-0.80). The area under the curve (AUC) of HDL-c + tumor size + age was 0.85 (95% CI: 0.79-0.91) in identifying G2/G3 PNENs, and HDL-c (> 0.9 mmol/L) + tumor size + age had an AUC of 0.77 (95% CI: 0.70-0.84) in identifying G3 PNENs. HDL-c level was associated with lymph node metastasis (OR = 0.24, 95%CI:0.08-0.99). CONCLUSION: Serum HDL-c levels were significantly associated with malignant behaviors in PNENs, in particular to tumor grade and lymph node metastasis.