Single-cell genomics and regulatory networks for 388 human brains.

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet, little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multi-omics datasets into a resource comprising >2.8M nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550K cell-type-specific regulatory elements and >1.4M single-cell expression-quantitative-trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

ScISOr-ATAC reveals convergent and divergent splicing and chromatin specificities between matched cell types across cortical regions, evolution, and in Alzheimer's Disease.

Multimodal measurements have become widespread in genomics, however measuring open chromatin accessibility and splicing simultaneously in frozen brain tissues remains unconquered. Hence, we devised Single-Cell-ISOform-RNA sequencing coupled with the Assay-for-Transposase-Accessible-Chromatin (ScISOr-ATAC). We utilized ScISOr-ATAC to assess whether chromatin and splicing alterations in the brain convergently affect the same cell types or divergently different ones. We applied ScISOr-ATAC to three major conditions: comparing (i) the Rhesus macaque (Macaca mulatta) prefrontal cortex (PFC) and visual cortex (VIS), (ii) cross species divergence of Rhesus macaque versus human PFC, as well as (iii) dysregulation in Alzheimer's disease in human PFC. We found that among cortical-layer biased excitatory neuron subtypes, splicing is highly brain-region specific for L3-5/L6 IT_RORB neurons, moderately specific in L2-3 IT_CUX2.RORB neurons and unspecific in L2-3 IT_CUX2 neurons. In contrast, at the chromatin level, L2-3 IT_CUX2.RORB neurons show the highest brain-region specificity compared to other subtypes. Likewise, when comparing human and macaque PFC, strong evolutionary divergence on one molecular modality does not necessarily imply strong such divergence on another molecular level in the same cell type. Finally, in Alzheimer's disease, oligodendrocytes show convergently high dysregulation in both chromatin and splicing. However, chromatin and splicing dysregulation most strongly affect distinct oligodendrocyte subtypes. Overall, these results indicate that chromatin and splicing can show convergent or divergent results depending on the performed comparison, justifying the need for their concurrent measurement to investigate complex systems. Taken together, ScISOr-ATAC allows for the characterization of single-cell splicing and chromatin patterns and the comparison of sample groups in frozen brain samples.

scENCORE: leveraging single-cell epigenetic data to predict chromatin conformation using graph embedding.

Dynamic compartmentalization of eukaryotic DNA into active and repressed states enables diverse transcriptional programs to arise from a single genetic blueprint, whereas its dysregulation can be strongly linked to a broad spectrum of diseases. While single-cell Hi-C experiments allow for chromosome conformation profiling across many cells, they are still expensive and not widely available for most labs. Here, we propose an alternate approach, scENCORE, to computationally reconstruct chromatin compartments from the more affordable and widely accessible single-cell epigenetic data. First, scENCORE constructs a long-range epigenetic correlation graph to mimic chromatin interaction frequencies, where nodes and edges represent genome bins and their correlations. Then, it learns the node embeddings to cluster genome regions into A/B compartments and aligns different graphs to quantify chromatin conformation changes across conditions. Benchmarking using cell-type-matched Hi-C experiments demonstrates that scENCORE can robustly reconstruct A/B compartments in a cell-type-specific manner. Furthermore, our chromatin confirmation switching studies highlight substantial compartment-switching events that may introduce substantial regulatory and transcriptional changes in psychiatric disease. In summary, scENCORE allows accurate and cost-effective A/B compartment reconstruction to delineate higher-order chromatin structure heterogeneity in complex tissues.

Mitigating Effect of Matricin against Benzo(a)pyrene-induced Lung Carcinogenesis in Experimental Mice Model.

BACKGROUND: Lung cancer is a life-threatening disease that is still prevalent worldwide. This study aims to evaluate the effects of matricin, a sesquiterpene, on the carcinogenic agent benzo(a)pyrene [B(a)P]-induced lung cancer in Swiss albino mice. METHODS: Lung cancer was induced by oral administration of B(a)P at 50 mg/kg b. wt. in model Swiss-albino mice (group II) as well in experimental group III, and treated with matricin (100 mg/kg b. wt.) in group III. Upon completion of treatment for 18 weeks, the changes in body weight, tumor formation, enzymatic and non-enzymatic antioxidant levels (GSH, SOD, GPx, GR, QR, CAT), lipid peroxidation (LPO) level, pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß), immunoglobulin levels (IgG, IgM), apoptosis markers (Bax, Bcl-xL), tumor markers (carcinoembryogenic antigen (CEA), neuron-specific enolase (NSE)), and histopathological (H&E) alterations were determined. RESULTS: The results indicate that B(a)P caused a significant increase of tumor formation in the lungs, increased tumor markers and inflammatory cytokines in serum, and depletion of enzymatic/ non-enzymatic antioxidants and immunoglobulins, compared to the untreated control group. Matricin treatment significantly reversed the changes caused by B(a)P as evidenced by the biochemical and histopathological assays. CONCLUSION: The changes caused by matricin clearly indicate the cancer-preventive effects of matricin against B(a)P-induced lung cancer in animal models, which can be attributed to the antioxidant activity, immunomodulation, and mitigation of the NF-kß pathway.

A right convergence area of the prefrontal lobe is involved in the improvement of semantic fluency in patients with post-stroke aphasia.

OBJECTIVES: This study aimed to longitudinally observe the improvement mechanism of semantic fluency in subacute post-stroke aphasia (PSA) patients using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Twelve PSA patients, about one month after onset, were enrolled in this study and received speech-language therapy (SLT) for one month. Auditory comprehension and semantic fluency were evaluated using the Western Aphasia Battery (WAB) and the Animal Fluency Test. Before and after treatment, rs-fMRI data were collected, and the dice similarity coefficient was used to measure the spatial similarity between each patient's lesion and a reference lesion. The left posterior inferior temporal gyrus (pITG) was used as a seed to calculate the normalized functional connectivity in whole-brain voxel analysis using DPABI software for statistical analysis. RESULTS: The dice similarity coefficient between each patient's lesion and the reference lesion showed moderate to high intensity (0.57 ± 0.14) in the Montreal Neurological Institute space. After treatment, we found a significant increase in functional connectivity between the left pITG and the right prefrontal lobe convergence area (peak t = 8.219, Gaussian random field multiple comparison correction, voxel p < 0.001, cluster p < 0.05). The increase in functional connectivity was negatively correlated with the improvement in auditory comprehension (r =-0.707, p = 0.033) and positively correlated with the improvement in semantic fluency (r = 0.79, p = 0.02). CONCLUSION: The improvement of semantic fluency in subacute PSA patients may require the participation of the right convergence area of the prefrontal lobe.

The emotion prediction of college students with attention LSTM during the COVID19 epidemic.

During the COVID19 pandemic, there is a pronounced collective mental health issue among college students. Forecasting the trend of emotional changes in on-campus students is crucial to effectively address this issue. This study proposes an Attention-LSTM neural network model that performs deep learning on key input sequence information, so as to predict the distribution of emotional states in college students. By testing 60 consecutive days of emotional data, the model successfully predicts students' emotional distribution, triggers and resolution strategies, with an accuracy rate of no less than 99%. Compared with models such as ARIMA, SARIMA and VAR, this model shows significant advantages in accuracy, operational efficiency, and data collection requirements. The integration of deep learning technology with student management in this study offers a novel approach to address emotional issues among students under exceptional circumstances.

Bulk Passivation Enables Hundredfold-Enhanced Electroluminescence of Monophosphine Cu4 I4 Cubes.

Electroluminescent (EL) clusters emerged rapidly, owing to their organic-inorganic hybrid character useful for comprehensive performance integration and the potential for large-scale display and lighting applications. However, despite their good photoluminescent (PL) properties, until present, no efficient EL monodentate ligand-based clusters were reported due to structural variation during processing and excitation and exciton confinement on cluster-centered quenching states. Here we demonstrate an effective bulky passivation strategy for efficient cluster light-emitting diodes with a monophosphine Cu4 I4 cube named [TMeOPP]4 Cu4 I4 . With terminal pyridine groups, an active matrix named TmPyPB supports an effective host-cluster interplay for configuration fixation, structural stabilization, and exciton-confinement optimization. Compared to common inactive hosts, the passivation effects of TmPyPB markedly reduce trap-state densities by 24-40 % to suppress nonradiative decay, resulting in state-of-the-art PL and EL quantum yields reaching 99 % and 15.6 %, respectively, which are significantly improved by about 7-fold. TmPyPB simultaneously increases EL luminance to 104 nits, which is ≈100-fold that of the non-doped analogue.

Naples Prognostic Score is an Independent Prognostic Factor in Patients with Small Cell Lung Cancer and Nomogram Predictive Model Established.

Background: The routine clinical nutritional and inflammatory indicators such as serum albumin, total cholesterol and lymphocytes have been widely investigated in the prognosis of small cell lung cancer (SCLC). The Naples prognostic score (NPS), based on nutritional and inflammatory status, has been identified as a prognostic impactor in several malignancies. However, the prognostic role of NPS in SCLC has not been elucidated. This study aims to evaluate the prognostic effect of NPS in SCLC patients. Patients and Methods: Patients with SCLC were recruited at Hebei General Hospital between April 2015 and August 2021. Pretreatment clinical and laboratory data were obtained. Participants were assigned into three groups according to NPS (group 0: NPS=0, group 1: NPS=1 or 2, group 2: NPS=3 or 4). Kaplan-Meier and Cox regression analysis were performed to assess the prognostic significance of NPS. The RMS package in R software was used to draw the nomogram predictive model. Results: A total of 128 patients were enrolled. The median progression-free survival (PFS) and overall survival (OS) was 7.2 and 12.3 months, respectively. The median PFS and OS was 12.3 vs 19.8 months, 7.6 vs 14.1 months and 6.0 vs 8.45 months for the three groups respectively. There were significant differences in both OS and FPS among the three groups. Survival analysis showed that NPS was significantly correlated with both OS and PFS (P<0.05). Lower NPS is associated with longer OS and PFS. Multivariate analysis showed that NPS has an independent prognostic impact on OS (P<0.05). The nomogram predictive model showed that NPS has good predictive power for survival rates. Conclusion: NPS is an independent prognostic factor for OS in SCLC patients. Low NPS may predict longer OS. Therefore NPS plays a vital role in the nomogram predictive model of survival rates in SCLC patients.

Expediting knowledge acquisition by a web framework for Knowledge Graph Exploration and Visualization (KGEV): case studies on COVID-19 and Human Phenotype Ontology.

BACKGROUND: Knowledges graphs (KGs) serve as a convenient framework for structuring knowledge. A number of computational methods have been developed to generate KGs from biomedical literature and use them for downstream tasks such as link prediction and question answering. However, there is a lack of computational tools or web frameworks to support the exploration and visualization of the KG themselves, which would facilitate interactive knowledge discovery and formulation of novel biological hypotheses. METHOD: We developed a web framework for Knowledge Graph Exploration and Visualization (KGEV), to construct and visualize KGs in five stages: triple extraction, triple filtration, metadata preparation, knowledge integration, and graph database preparation. The application has convenient user interface tools, such as node and edge search and filtering, data source filtering, neighborhood retrieval, and shortest path calculation, that work by querying a backend graph database. Unlike other KGs, our framework allows fast retrieval of relevant texts supporting the relationships in the KG, thus allowing human reviewers to judge the reliability of the knowledge extracted. RESULTS: We demonstrated a case study of using the KGEV framework to perform research on COVID-19. The COVID-19 pandemic resulted in an explosion of relevant literature, making it challenging to make full use of the vast and heterogenous sources of information. We generated a COVID-19 KG with heterogenous information, including literature information from the CORD-19 dataset, as well as other existing knowledge from eight data sources. We showed the utility of KGEV in three intuitive case studies to explore and query knowledge on COVID-19. A demo of this web application can be accessed at http://covid19nlp.wglab.org . Finally, we also demonstrated a turn-key adaption of the KGEV framework to study clinical phenotypic presentation of human diseases by Human Phenotype Ontology (HPO), illustrating the versatility of the framework. CONCLUSION: In an era of literature explosion, the KGEV framework can be applied to many emerging diseases to support structured navigation of the vast amount of newly published biomedical literature and other existing biological knowledge in various databases. It can be also used as a general-purpose tool to explore and query gene-phenotype-disease-drug relationships interactively.

Translator: A Transfer Learning Approach to Facilitate Single-Cell ATAC-Seq Data Analysis from Reference Dataset.

Recent advances in single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) have allowed simultaneous epigenetic profiling over thousands of individual cells to dissect the cellular heterogeneity and elucidate regulatory mechanisms at the finest possible resolution. However, scATAC-seq is challenging to model computationally due to the ultra-high dimensionality, low signal-to-noise ratio, complex feature interactions, and high vulnerability to various confounding factors. In this study, we present Translator, an efficient transfer learning approach to capture generalizable chromatin interactions from high-quality (HQ) reference scATAC-seq data to obtain robust cell representations in low-to-moderate quality target scATAC-seq data. We applied Translator on various simulated and real scATAC-seq datasets and demonstrated that Translator could learn more biologically meaningful cell representations than other methods by incorporating information learned from the reference data, thus facilitating various downstream analyses such as clustering and motif enrichment measurements. Moreover, Translator's block-wise deep learning framework can handle nonlinear relationships with restricted connections using fewer parameters to boost computational efficiency through Graphics Processing Unit (GPU) parallelism. Finally, we have implemented Translator as a free software package available for the community to leverage large-scale, HQ reference data to study target scATAC-seq data.

InsuLock: A Weakly Supervised Learning Approach for Accurate Insulator Prediction, and Variant Impact Quantification.

Mapping chromatin insulator loops is crucial to investigating genome evolution, elucidating critical biological functions, and ultimately quantifying variant impact in diseases. However, chromatin conformation profiling assays are usually expensive, time-consuming, and may report fuzzy insulator annotations with low resolution. Therefore, we propose a weakly supervised deep learning method, InsuLock, to address these challenges. Specifically, InsuLock first utilizes a Siamese neural network to predict the existence of insulators within a given region (up to 2000 bp). Then, it uses an object detection module for precise insulator boundary localization via gradient-weighted class activation mapping (~40 bp resolution). Finally, it quantifies variant impacts by comparing the insulator score differences between the wild-type and mutant alleles. We applied InsuLock on various bulk and single-cell datasets for performance testing and benchmarking. We showed that it outperformed existing methods with an AUROC of ~0.96 and condensed insulator annotations to ~2.5% of their original size while still demonstrating higher conservation scores and better motif enrichments. Finally, we utilized InsuLock to make cell-type-specific variant impacts from brain scATAC-seq data and identified a schizophrenia GWAS variant disrupting an insulator loop proximal to a known risk gene, indicating a possible new mechanism of action for the disease.

Integrating longitudinal clinical and microbiome data to predict growth faltering in preterm infants.

Preterm birth affects more than 10% of all births worldwide. Such infants are much more prone to Growth Faltering (GF), an issue that has been unsolved despite the implementation of numerous interventions aimed at optimizing preterm infant nutrition. To improve the ability for early prediction of GF risk for preterm infants we collected a comprehensive, large, and unique clinical and microbiome dataset from 3 different sites in the US and the UK. We use and extend machine learning methods for GF prediction from clinical data. We next extend graphical models to integrate time series clinical and microbiome data. A model that integrates clinical and microbiome data improves on the ability to predict GF when compared to models using clinical data only. Information on a small subset of the taxa is enough to help improve model accuracy and to predict interventions that can improve outcome. We show that a hierarchical classifier that only uses a subset of the taxa for a subset of the infants is both the most accurate and cost-effective method for GF prediction. Further analysis of the best classifiers enables the prediction of interventions that can improve outcome.

Effect of microRNA-181b on the biological characteristics and clinical drug resistance of small-cell lung cancer by targeting angiotensin converting enzyme 2.

OBJECTIVE: To clarify the effect of miR-181b on the biological function of small-cell lung cancer (SCLC) and explore the effect of clinical resistance on SCLC. METHODS: Blood samples were collected from 30 SCLC patients and 30 non-SCLC patients in our department from 2017 to 2019 to detect the expression level of miR-181b.The expression level of miR-181b was detected in SCLC cells by RT-PCR, and screening of downstream target genes by gene chip, verification with luciferase, and Western blotting. In addition, collect the general data of 30 SCLC patients and 30 non-SCLC patients (control group), the patients were diagnosed by pathology and undergoing EC protocol in the Department of Thoracic Surgery and Oncology of our hospital to detect the expression level of mir-181b in different periods. Furthermore, in the SCLC cell line, EC chemotherapy was administered to detect the sensitivity of drug resistance and nondrug resistance. RESULTS: miR-181b in SCLC patients was lower than in normal people as well as the drug-sensitive cell line. ACE2 was verified as a downstream target of miR-181b by gene chip screening. First-line chemotherapy can promote the recovery of miR-181b, but cannot repair to normal levels. miR-181b can enhance the drug sensitivity of SCLC drug-resistant cells. CONCLUSION: miR-181b directly targets ACE2 to affect the biological characteristics of SCLC. The expression level of miR-181b is highly related to the drug resistance of SCLC, which suggests that miR-181b could be a potential biomarker candidate for treatment efficacy of SCLC.

Improvement in language function in patients with aphasia using computer-assisted executive function training: A controlled clinical trial.

BACKGROUND: Nonverbal cognitive training for aphasia has gained popularity. Prior research has found that cognitive status correlates with language function. OBJECTIVE: To determine whether nonverbal computer-assisted executive control training (CAET) to improve cognitive status affects language performance in patients with aphasia (PWA) and executive dysfunction. DESIGN: A single blind randomized trial. SETTING: Department of Rehabilitation, Affiliated Hospital of Xuzhou Medical University. PARTICIPANTS: A total of 68 individuals were randomized, underwent treatment and were included in the analysis (CAET group, n = 33; control group, n = 35). INTERVENTIONS: The experimental group was treated with 4 weeks of traditional speech and language therapy (SLT) combined with CAET. The control group underwent SLT only. MAIN OUTCOME MEASURES: Western Aphasia Battery [WAB]) with executive dysfunction (as assessed by the verbal fluency test [VFT], the Proverbs Test, the Tower of London Test [TLT], the Stroop Color and Word Test [SCWT], and the Trail Making Test [TMT]). RESULTS: Differences between pre- and posttreatment language outcomes except oral naming (group × time, p = .236) were significantly greater in the experimental group compared with the control group: spontaneous speech (group × time, p = .026), auditory comprehension (group × time, p < .001), speech repetition (group × time, p = .001), and aphasia quotient (AQ; group × time, p < .001). A similar effect was observed for cognitive function such as Trial Making Test (TMT)-A (group × time, p = .006), TMT-B (group × time, p = .005), and verbal fluency test (VFT-V; group × time, p = .018). CONCLUSION: The study demonstrates that CAET combined with SLT can yield favorable language outcomes for PWA, especially improvements in auditory comprehension and AQ. CAET combined with SLT generates benefits in both cognitive function and language performance.

Efficacy of Acupuncture Combined with Rehabilitation Training for Intensive Care Unit-Acquired Muscle Weakness: A Protocol for a Randomized, Sham-Procedure-Controlled Clinical Trial.

To evaluate the efficacy of acupuncture combined with rehabilitation training in patients with intensive care unit (ICU)-acquired muscle weakness (ICUAW), a single-blinded, randomized, sham-controlled clinical trial is designed for execution. In total, 56 participants with ICUAW will be randomly assigned to the treatment and control groups with 28 participants in each group. The participants will be treated with acupunctures or sham procedures at LI15, LI11, ST36, GB34, and ST31, 5 times per week for a total of 20 sessions in 4 weeks while they will receive rehabilitation training. Patients will be followed up every month for 3 months after treatment. The primary outcomes include changes in quadriceps femoris muscle area, thickness, vastus intermediate muscle thickness, subcutaneous tissue thickness, and ultrasonic intensities of the rectus femoris. The secondary outcomes consist of the modified Barthel index score and the Medical Research Council total score. Participants' mechanical ventilation, the rate of detachment at the second week, the 28-day survival rate, and the occurrence of adverse reactions will be measured, and any side effects will be reported and recorded. Patient outcomes between the treatment and control groups will be compared and statistically tested. We anticipate that the therapeutic regimen of acupuncture combined with rehabilitation training would be more effective than the rehabilitation training alone for the treatment of the ICUAW. The findings of this study could help develop a better strategy for the treatment of the ICUAW disease and explore a clinical application of an acupuncture technique. Trial registration: Chinese Clinical Trial Register ChiCTR2000038779. Registered 30 September, 2020, https://www.chictr.org.cn/showproj.aspx?proj=62284.

Leaching and In Vivo Bioavailability of Antimony in PET Bottled Beverages.

Antimony (Sb) may leach from polyethylene terephthalate (PET) materials into bottled water under improper storage conditions, particularly at high temperatures, leading to potential Sb chronic exposure and adverse health effects. However, Sb leaching may be promoted by various beverage constituents, which has received limited attention to date. In addition, few studies have considered Sb bioavailability in beverages and the influence of the beverage matrix on Sb bioavailability. In this study, PET-bottled beverages (n = 50) covering six categories (namely, carbonated, fruit juices, tea, sports, protein, and coffee beverages) were explored. Antimony leaching was assessed following the incubation of beverages at 60 °C for 7 days, which resulted in Sb concentrations 1.10-10.9 times greater than concentrations observed pre-incubation. Although regulatory standards vary internationally, a total of 21 beverages exceeded the Japanese Sb drinking water standard of 2 µg/L (up to 4.08 ± 0.11 µg/L) following incubation at 60 °C. pH significantly influenced Sb leaching (r = -0.38, p = 0.007) with beverages displaying lower pH (e.g., carbonated drinks) exhibiting higher Sb concentrations. An in vivo mouse model, using the liver as the biological endpoint, was adopted to assess Sb relative bioavailability (RBA) in bottled beverages. Sb RBA ranged from 1.97-58.7% with coffee beverages exhibiting the lowest Sb RBA (1.97-13.7%) and protein drinks the highest (41.1-58.7%). Linear regression revealed that Sb RBA in beverages was negatively influenced by Fe (r = -0.69, p = 0.02) and P (r = -0.73, p = 0.01) concentrations but positively correlated with tartaric acid (r = 0.59, p = 0.02). When an exposure assessment was undertaken using data generated in this study, carbonated and protein-rich beverages exhibited a higher exposure risk due to elevated Sb leaching and high Sb RBA compared to other beverage categories.

Feasibility of Distal Radial Access for Coronary Angiography and Percutaneous Coronary Intervention: A Single Center Experience.

OBJECTIVE: Asymptomatic radial artery occlusion remains the most common complication in transradial coronary interventional procedure. To prevent radial artery occlusion, distal transradial access (dTRA) has been suggested recently. In this article, we aim to describe our experience and to assess feasibility and safety of this new access site for routine coronary angiography (CAG) and percutaneous coronary intervention (PCI). METHODS: We retrospective analyzed 1,063 consecutive patients who were assigned to undergo CAG or procedural PCI through dTRA between 1 January 2018 and 31 December 2019 at Affiliated Zhongshan Hospital of Dalian University. The size of radial sheath used was 5 or 6 French. The sheath was removed at procedure termination, and hemostasis was obtained by compression bandage with gauze. The success rate of dTRA access defined by successful radial artery cannulation on the first dTRA side attempted, the cause of access failure, the hemostasis duration, the incidence of post-catheterization radial artery occlusion, and the other access-related complications including hematoma of forearm and thumb numbness were assessed. RESULTS: Radial artery cannulation via dTRA was successful in 953 of 1,063 patients with a success rate of 89.7%. Mean age of successful cases was 64.6 ± 11.2 years (26-94 years) with 339 (35.6%) women. A total of 363 (38.1%) cases were PCI. Among them, 95 cases (10%) underwent urgent PCI, including primary PCI in 64 patients with ST-segment elevation myocardial infarction and immediate PCI (<2 h from hospital admission) in 31 patients with very high-risk non-ST-segment elevation acute coronary syndrome. A total of 269 (28.2%) cases were via left dTRA. The 6 French sheath was used in 602 (63.2%) cases. Hemostasis was obtained within 2 h in 853 (89.5%) patients. There were 110 (10.3%) procedural failures: 59 (5.6%) cases of artery puncture failure, 49 (4.9%) cases of guide wire insertion failure, and 2 (0.2%) cases of sheath insertion failure. Complications potentially related to distal radial access included radial artery occlusion at the access site (13 cases, 1.4%), forearm radial artery occlusion (4 cases, 0.4%), hematoma of forearm (5 cases, 0.5%), and transient thumb numbness (2 cases, 0.2%). CONCLUSION: dTRA is a feasible and safe access and can be used as a rational alternative to traditional radial access for routine coronary interventional procedure.

Sarpogrelate and rosuvastatin synergistically ameliorate aortic damage induced by hyperlipidemia in apolipoprotein E-deficient mice.

The current study aimed to investigate whether sarpogrelate and rosuvastatin possess anti-arterial injury, and attempted to elucidate the mechanism of action underlying this activity. Sarpogrelate, a 5-hydroxytryptamine type 2A antagonist, is extensively used to prevent arterial thrombosis; however, its effects on atherosclerosis remain unknown. In the present study, sarpogrelate combined with rosuvastatin or rosuvastatin alone were administered to male ApoE-/- mice fed a high-fat diet (HFD) for 8 weeks. Metabolic parameters in the blood samples were analyzed using an automatic analyzer. Aortic tissues were stained with hematoxylin and eosin for morphological analysis. The expression levels of oxidized-low density lipoprotein (LDL) specific scavenging receptors, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and cluster of differentiation 68 were detected via immunostaining. mRNA expression levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α were determined via reverse transcription-quantitative PCR analysis, while protein expression levels of LOX-1 and phosphor(p)-ERK were determined via western blot analysis. The results demonstrated that sarpogrelate combined with rosuvastatin treatment significantly decreased total cholesterol and LDL cholesterol levels in the serum, and alleviated intimal hyperplasia and lipid deposition, accompanied by decreased inflammatory cell infiltration and lower expression levels of inflammatory cytokines, compared with rosuvastatin monotherapy or HFD treatment. Furthermore, sarpogrelate combined with rosuvastatin treatment significantly decreased the expression levels of LOX-1 and p-ERK. Taken together, these results suggest that the positive effects of sarpogrelate combined with rosuvastatin treatment on aortic injury may be associated with the regulation of the LOX-1/p-ERK signaling pathway. Sarpogrelate and rosuvastatin synergistically decreased aortic damage in ApoE-/- HFD mice, and thus provide a basis for the treatment of aortic injury caused by hyperlipidemia with sarpogrelate.

Efficacy of acupuncture at three nasal acupoints plus acupoint application for perennial allergic rhinitis: A multicenter, randomized controlled trial protocol.

BACKGROUND: Many studies have shown the potential therapeutic effect of acupuncture on allergic rhinitis. Most of these studies were limited by low-quality evidence. Preliminary experiments showed that the use of acupuncture at three nasal acupoints plus acupoint application (AAP) achieves a more persistent effect in the treatment of perennial allergic rhinitis than acupuncture alone. In this study, a multicenter, single-blind, randomized controlled trial will be performed, in which acupuncture at nonmeridian acupoints and sham AAP will be used as the control group to evaluate the effect of AAP through long-term observation. METHODS: The trial is designed on the basis of the Consolidated Standards of Reporting Trials 2010 guidelines and Standards for Reporting Interventions in Controlled Trials of Acupuncture. A total of 120 participants with perennial allergic rhinitis will be randomly assigned to a treatment or control group. A specially appointed investigator will be in charge of randomization. The participants in the treatment group will be treated with acupuncture at EX-HN3, LI20, and EX-HN8 thrice per week for a total of 12 sessions. In addition, they will undergo AAP at DU14, BL13, EX-BI, and RN22. The participants in the control group will be treated with sham AAP. The primary outcome will be the change in the Total Nasal Symptom Score from baseline to the completion of 4-week treatment. Secondary outcomes include changes in visual analog scale and total non-nasal symptom scores from baseline to the second and fourth weeks of treatment, as well as 1, 3, and 6 months after the completion of treatment. Peripheral blood IL-4, IL-5, IL-6, IL-8, and IL-10 levels will be measured, and any side effects related to treatment will be observed and recorded. DISCUSSION: It is expected that this randomized clinical trial will provide evidence to determine the effects of AAP compared with acupuncture at nonmeridian acupoints and sham AAP, particularly the long-term effect. These findings will help improve the clinical application of this technique. TRIAL REGISTRATION: Acupuncture-Moxibustion Clinical Trial Registry AMCTR-ICR-18000179. Registered on 12 April 2018.

[A case-control study on the treatment of carpal tunnel syndrome with needle Dao].

OBJECTIVE: To study clinical effects of needle Dao for the treatment of carpal tunnel syndrome. METHODS: From July 2014 to December 2016, 60 patients with carpal tunnel syndrome were divided into two groups: needle Dao treatment group(treatment group), and brace and medicine treatment group(control group), 30 cases in each group. There were 8 males and 22 females in the treatment group, with an average age of (49.38±7.43) years old. There were 7 males and 23 females in the control group, with an average age of (50.23±8.71) years old. There were no statistically significant differences between two groups before treatment in age, sex, course of disease, sensory nerve conduction velocity (SCV), sensory nerve action potential (SNAP), and distal motor latency(DML). The patients in the treatment group were treated with needle Dao for 1 to 2 times, while the patients in the control group were given celecoxib, vitamin B1 and vitamin B12, with the brace fixed. After treatment, the changes of SCV, SNAP and DML in two groups were observed. RESULTS: After treatment, the SCV were (48.63±7.33) m/s and (41.24±6.15) m/s in treatment group and control group separately, the SNAP were (9.89±3.71) m/s and (8.22±2.19) m/s, and the DML were(5.11±2.28) m/s and (6.13±2.23) m/s. The SCV, SNAP and DML after treatment were better than those before treatment(P<0.05). And the results of SCV, SNAP and DML of patients in the treatment group were better than those of patients in the control group(P<0.001). CONCLUSIONS: Needle Dao can effectively improve the overall treatment efficiency of patients with carpal tunnel syndrome and reduce the symptoms of patients, which is feasible and suitable to use in clinical.