Factors associated with SARS-CoV-2 vaccine hesitancy after stroke: a cross-sectional study.

BACKGROUND: The vaccination status of post-stroke patients, who are at high risk of severe outcomes from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a significant concern, yet it remains unclear. We aimed to explore the vaccination status, factors associated with vaccine hesitancy, and adverse effects after vaccination among post-stroke patients. METHODS: This multi-center observational study enrolled hospitalized post-stroke patients from six Chinese hospitals (Oct 1, 2020 - Mar 31, 2021), examining vaccine uptake and self-reported reasons for vaccine hesitancy, utilizing logistic regression to investigate risk factors for vaccine hesitancy, and recording any adverse reactions post-vaccination. RESULTS: Of the total 710 post-stroke patients included in the study, 430 (60.6%) had completed the recommended full-3 dose SARS-CoV-2 vaccination, with 176 (24.8%) remaining unvaccinated. The most common reasons for vaccine hesitancy were concerns about vaccine side effects (41.5%) and impaired mobility (33.9%). Logistic regression identified advanced age (aOR = 1.97, 95%CI: 1.36-2.85, P = 0.001), lower Barthel Index score (aOR = 0.88, 95%CI: 0.82-0.93, P = 0.018), higher Modified Rankin Scale score (aOR = 1.85, 95%CI: 1.32-2.56, P = 0.004), and poorer usual activity level of EuroQol 5-Dimension (aOR = 2.82, 95%CI: 1.51-5.28, P = 0.001) as independent risk factors for vaccine hesitancy. Approximately 14.8% reported minor adverse reactions, mainly pain at the injection site. CONCLUSION: We found that post-stroke patients have insufficient SARS-CoV-2 vaccination rates, with key risk factors for vaccine hesitancy including concerns about side effects, advanced age, and functional impairments. No severe adverse reactions were observed among the vaccinated population.

Alleviating Recombinant Tissue Plasminogen Activator-induced Hemorrhagic Transformation in Ischemic Stroke via Targeted Delivery of a Ferroptosis Inhibitor.

Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) is the primary treatment for ischemic stroke. However, rtPA treatment can substantially increase blood-brain barrier (BBB) permeability and susceptibility to hemorrhagic transformation. Herein, the mechanism underlying the side effects of rtPA treatment is investigated and demonstrated that ferroptosis plays an important role. The ferroptosis inhibitor, liproxstatin-1 (Lip) is proposed to alleviate the side effects. A well-designed macrocyclic carrier, glucose-modified azocalix[4]arene (GluAC4A), is prepared to deliver Lip to the ischemic site. GluAC4A bound tightly to Lip and markedly improved its solubility. Glucose, modified at the upper rim of GluAC4A, imparts BBB targeting to the drug delivery system owing to the presence of glucose transporter 1 on the BBB surface. The responsiveness of GluAC4A to hypoxia due to the presence of azo groups enabled the targeted release of Lip at the ischemic site. GluAC4A successfully improved drug accumulation in the brain, and Lip@GluAC4A significantly reduced ferroptosis, BBB leakage, and neurological deficits induced by rtPA in vivo. These findings deepen the understanding of the side effects of rtPA treatment and provide a novel strategy for their effective mitigation, which is of great significance for the treatment and prognosis of patients with ischemic stroke.

Gut microbiota-host lipid crosstalk in Alzheimer's disease: implications for disease progression and therapeutics.

Trillions of intestinal bacteria in the human body undergo dynamic transformations in response to physiological and pathological changes. Alterations in their composition and metabolites collectively contribute to the progression of Alzheimer's disease. The role of gut microbiota in Alzheimer's disease is diverse and complex, evidence suggests lipid metabolism may be one of the potential pathways. However, the mechanisms that gut microbiota mediate lipid metabolism in Alzheimer's disease pathology remain unclear, necessitating further investigation for clarification. This review highlights the current understanding of how gut microbiota disrupts lipid metabolism and discusses the implications of these discoveries in guiding strategies for the prevention or treatment of Alzheimer's disease based on existing data.

Knowledge mapping of trends and hotspots in the field of exercise and cognition research over the past decade.

Exercise elicits a wide range of physiological responses in mammalian tissues that enhance a broad range of functions, particularly in improving cognitive performance. However, the field lacks a comprehensive bibliometric analysis that clarifies its knowledge structure and research hotspots. This study aims to address this gap and map the research landscape regarding the role of exercise in cognitive function enhancement. Firstly, the frequencies and co-occurrence of keywords were analysed to identify six main clusters: aging, cognitive impairment, rehabilitation, obesity, fatigue, and hippocampus. Secondly, reference timeline co-citation analysis revealed that hippocampus and aging were the major bursts with high intensity and long attention span while children had recently emerged as a topical subject. Finally, the evolution of themes from 2012 to 2022 was analysed, and found that older adults had been the leading research theme for exercise affecting cognition. Childhood obesity was an emerging theme that attracted increasing research attention in recent years while the hippocampus research theme expanded rapidly during the decade but remained a niche topic with less relevance to others. This research identified and summarised research priorities and evolutionary trends in exercise to improve cognition by constructing knowledge networks through visual analysis. It provides researchers with a comprehensive insight into the current state of the field to facilitate further research.

Knowledge mapping of exercise and physical activity research in older adults: Hotspots, bursts, and trends of the last decade.

Background and objectives: Global aging has increased the importance of health management in older adults. Exercise is a crucial strategy for healthy aging and has led to numerous scientific advancements due to its impact on age-related illnesses. We aim to investigate the research hotspots, bursts of knowledge base, and trends in the field of exercise and physical activity in older adults over the past decade and present them in a visual manner. Methods: We searched and retrieved data from the Web of Science database, and performed a bibliometric analysis of publications on exercise and physical activity research in older adults from 2013 to 2022. We evaluated the current status and hotspots through co-occurrence analysis using VOSviewer. The evolution and bursts of knowledge base were assessed through co-citation analysis using CiteSpace. Thematic evolution was analyzed using the bibliometrix package to discover keyword trends. The attribution and collaboration of countries/regions, institutions and authors were also analyzed. Results: A total of 27,820 publications were included. Publications on exercise and physical activity in older adults increased from 1755 records in 2013-3737 records in 2022 annually. In co-occurrence analysis of keywords, 5 major clusters were revealed: sarcopenia, cognition, frailty, mental health, and rehabilitation. Co-citation analysis reveals that the knowledge base has evolved from references focused on frailty, dementia, and physical activity before 2016 to references focus on sarcopenia, cognition and sedentary behavior after 2020. Among the top 10 high-frequency keywords, sarcopenia demonstrated a consistent and significant upward trend, with its percentage increasing from 8.7 % (82 times) in 2016 to 12.2 % (236 times) in the most recent year, making it the most frequently used keyword. Frailty ranked second, starting at 5.6 % (41 times) in 2013 and gradually rising to 11.7 % (225 times) in 2022. The most productive country, institution and author were the USA (8212 publications), the University of Pittsburgh(501 publications), and Brendon Stubbs(94 publications), respectively. Discussion: Publications on exercise and physical activity for older adults have surged in the last decade, accompanied by a shift in the knowledge base. Regional disparities in the academic output in this field need to be addressed in the future to promote healthy aging.

Associations of Blood and Cerebrospinal Fluid Aß and tau Levels with Renal Function.

Amyloid ß (Aß) and tau play pivotal roles in the pathogenesis of Alzheimer's disease (AD). Previous studies have shown that brain-derived Aß and tau can be cleared through transport into the periphery, and the kidneys may be vital organs involved in the clearance of Aß and tau. However, the effects of deficiency in the clearance of Aß and tau by the kidneys on brain AD-type pathologies in humans remain largely unknown. In this study, we first recruited 41 patients with chronic kidney disease (CKD) and 40 age- and sex-matched controls with normal renal function to analyze the associations of the estimated glomerular filtration rate (eGFR) with plasma Aß and tau levels. To analyze the associations of eGFR with cerebrospinal fluid (CSF) AD biomarkers, we recruited 42 cognitively normal CKD patients and 150 cognitively normal controls with CSF samples. Compared with controls with normal renal function, CKD patients had higher plasma levels of Aß40, Aß42 and total tau (T-tau), lower CSF levels of Aß40 and Aß42 and higher levels of CSF T-tau/Aß42 and phosphorylated tau (P-tau)/Aß42. Plasma Aß40, Aß42, and T-tau levels were negatively correlated with eGFR. In addition, eGFR was negatively correlated with CSF levels of T-tau, T-tau/Aß42, and P-tau/Aß42 but positively correlated with Mini-Mental State Examination (MMSE) scores. Thus, this study showed that the decline in renal function was correlated with abnormal AD biomarkers and cognitive decline, which provides human evidence that renal function may be involved in the pathogenesis of AD.

Circulating antibodies to Helicobacter pylori are associated with biomarkers of neurodegeneration in cognitively intact adults.

Helicobacter pylori (H. pylori) infection confers risk for Alzheimer's Disease (AD), with the mechanisms unknown. Infections are linked to the etiology of AD partly through modulating the humoral immunity post-infection. This study found increased plasma levels of tTau and pTau181 in H. Pylori infected individuals with intact cognition. Plasma antibodies to H. pylori were positively associated with Aß40, Aß42, tTau, and pTau181, adjusting for age, sex, education level, BMI, ApoE ε4 genotype, hypertension, diabetes mellitus, and hypercholesteremia. This study presents novel insights into the relationship between H. pylori infection and AD from an autoimmune perspective.

[Micronutrient Powders Feeding Behaviors of Baby Caregivers in Remote Rural Areas of Sichuan Province: A Study Based on the Theory of Reasoned Action].

Objective: To explore the status quo and influencing factors of feeding behaviors of micronutrient powders (MNP), or yingyangbao in Pinyin, the Chinese Romanization system, of baby caregivers in remote rural areas of Sichuan Province. Methods: In 2019, caregivers of babies aged 6 to 24 months from 6 counties of Sichuan Province were selected as the respondents of the survey through a multistage cluster random sampling method. Data concerning the baby caregivers' attitude of behavior, subjective norms, behavioral intention, and feeding behaviors about MNP feeding were collected with a questionnaire through a structured interview. Based on the theory of reasoned action, a structural equation model was constructed to explore the influencing factors of feeding behaviors. Results: A total of 1002 valid samples were included in the study. The effective feeding rate of MNP among the baby caregivers was 55.49%. The results of model analysis suggested that attitude of behavior ( ß direct=0.212, 95% CI: 0.105-0.327), subjective norm ( ß direct=0.123, 95% CI: 0.016-0.228), and behavioral intention ( ß direct=0.162, 95% CI: 0.093-0.224) could have a significant direct impact on MNP feeding behaviors. Behavior attitude ( ß indirect=0.044, 95% CI: 0.023-0.073) and subjective norms ( ß indirect=0.018, 95% CI: 0.001-0.040) could have a significant indirect impact on MNP feeding behaviors through the intermediary of behavioral intention. Among the three theoretical elements, attitude of behavior had the largest total effect on the feeding behavior ( ß total=0.256, 95% CI: 0.148-0.366). Conclusion: The effective feeding rate of MNP among baby caregivers in remote rural areas of Sichuan Province is low. The attitude of behavior and subjective norms of caregivers may have a direct impact on their feeding behavior, and both attitude of behavior and subjective norms can have an indirect impact on the feeding behavior through the intermediary of behavioral intention. The influence of attitude of behavior attitude on feeding behavior is greater than that of subjective norms. Future intervention plans for promoting effective MNP feeding should incorporate health education for baby caregivers and their important social relations. Thus, baby caregivers' attitude and willingness for MNP feeding will be strengthened and the effective feeding rate of MNP will be improved accordingly.

Pharmacokinetics, mass balance, and metabolism of [14C]TPN171, a novel PDE5 inhibitor, in humans for the treatment of pulmonary arterial hypertension.

TPN171 is a novel phosphodiesterase-5 (PDE5) inhibitor used to treat pulmonary arterial hypertension (PAH) and erectile dysfunction (ED), which currently is undergoing phase II clinical trials in China. In this single-center, single-dose, nonrandomized, and open design study, radiolabeled [14C]TPN171 was used to investigate the metabolic mechanism, pharmacokinetic characteristics, and clearance pathways of TPN171 in 6 healthy Chinese male volunteers. Each volunteer was administered a single oral suspension of 10 mg (100 µCi) of [14C]TPN171. We found that TPN171 was absorbed rapidly in humans with a peak time (Tmax) of 0.667 h and a half-life (t1/2) of approximately 9.89 h in plasma. Excretion of radiopharmaceutical-related components was collected 216 h after administration, accounting for 95.21% of the dose (46.61% in urine and 48.60% in feces). TPN171 underwent extensive metabolism in humans. Twenty-two metabolites were detected in human plasma, urine, and feces using a radioactive detector combined with a high-resolution mass spectrometer. According to radiochromatograms, a glucuronide metabolite of O-dealkylated TPN171 exceeded 10% of the total drug-related components in human plasma. However, according to the Food and Drug Administration (FDA) guidelines, no further tests are needed to evaluate the safety of this metabolite because it is a phase II metabolite, but the compound is still worthy of attention. The main metabolic biotransformation of TPN171 was mono-oxidation (hydroxylation and N-oxidation), dehydrogenation, N-dealkylation, O-dealkylation, amide hydrolysis, glucuronidation, and acetylation. Cytochrome P450 3A4 (CYP3A4) mainly catalyzed the formation of metabolites, and CYP2E1 and CYP2D6 were involved in the oxidative metabolism of TPN171 to a lesser extent. According to the incubation data, M1 was mainly metabolized to M1G by UDP-glucuronosyltransferase 1A9 (UGT1A9), followed by UGT1A7 and UGT1A10.

Ultrasonic-assisted stewing enhances the aroma intensity of chicken broth: A perspective of the aroma-binding behavior of fat.

This experiment investigated the underlying mechanism of ultrasonic-assisted stewing to enhance the aroma intensity of chicken broth by measuring fat content, oil droplet sizes, zeta potential, viscosity, surface protein loading, lipid oxidation, and aroma compound concentrations. As the thermo-ultrasound time increased, the fat content increased from 0.3 % to 1.2 %, resulting in a milky white appearance. After 1 h of thermo-ultrasound, the broth had the smallest particle size and the highest surface protein load, viscosity, and emulsion stability, as well as the highest total amount of aroma-active compounds of 314.70 ng/mg. With the further extension of thermo-ultrasound time, lipid oxidation increased, but the stability of chicken broth decreased, lowering the content of aroma-active compounds. These outcomes suggested that thermo-ultrasound could enhance the aroma intensity of chicken broth by increasing the fat content and the emulsion stability of the broth.

Identification and validation of autophagy-related genes during osteogenic differentiation of bone marrow mesenchymal stem cells.

Objectives: Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is an essential stage in bone formation. Autophagy plays a pivotal role in the self-renewal potential and pluripotency of stem cells. This study aimed to explore the function of autophagy-related genes during osteogenic differentiation of BMSCs. Materials and Methods: The differentially expressed autophagy-related genes (ARGs) were obtained from the GEO and HADb databases. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using R software. The PPI and hub gene mining networks were constructed using the STRING database and Cytoscape. Finally, the RT-qPCR was conducted to validate the expression level of ARGs in BMSCs. Results: Thirty-seven differentially expressed ARGs were finally obtained, including 12 upregulated and 25 downregulated genes. GO and KEGG enrichment analysis showed that most of these genes were enriched in apoptosis and autophagy. The PPI network revealed strong interactions between differentially expressed ARGs. The expression level of differentially expressed ARGs tested by RT-qPCR showed 6 upregulated ARGs, including FOXO1, MAP1LC3C, CTSB, FOXO3, CALCOCO2, FKBP1A, and 4 downregulated ARGs, including MAPK8IP1, NRG1, VEGFA, and ITGA6 were consistent with the expression of high-throughput sequencing data. Conclusion: We identified 37 ARGs during osteogenic differentiation using bioinformatics analysis. FOXO1, MAP1LC3C, CTSB, FOXO3, CALCOCO2, FKBP1A, MAPK8IP1, NRG1, VEGFA, and ITGA6 may regulate osteogenic differentiation of hBMSCs by involving autophagy pathway. This study provides new insight into the osteogenic differentiation of hBMSCs and may be available in developing therapeutic strategies for maxillofacial bone defects.

[Effect of Information Communication on Micronutrient Powders (or Yingyangbao) Feeding Behaviors of Different Generations of Baby Caregivers in Rural Areas].

Objective: To evaluate the status of information communication concerning micronutrient powders (MNP), or yingyangbao in Pinyin, the Chinese Romanization system, in areas covered by the Child Nutrition Improvement Project in a province in southwest China, and to investigate the effect of different communication channels and message communicated on the feeding behaviors of different generations of caregivers. Methods: In October 2019, 6 counties, including two counties with predominantly Han population, two counties with substantial Tibetan population, and two counties with substantial Yi population, were selected from a province in southwest China through multistage random cluster sampling. A total of 816 pairs of babies and their caregivers from 108 villages in 36 townships were enrolled for the study. The age of the babies ranged between 6 months to 24 months. A structured questionnaire concerning the demographic data of the babies and their caregivers, the communication channel of information on MNP and the message communicated, and the caregivers' MNP feeding behaviors was designed to collect data through face-to-face interviews. Logistic regression was done to analyze the effect of MNP information communication on the feeding behaviors of caregivers from different generations. Results: Caregivers acquired information on MNP from village and township physicians (85.66%), surrounding populations (15.81%), and brochures and mass media (4.78%). The messages they received included the free availability of MNP (37.50%), feeding methods (49.26%), and the benefits of giving babies MNP (57.84%). Among the caregivers, 89.95% knew about the availability of MNP, 69.73% were aware of the benefits, and 84.07% actually received MNP. The correct feeding rate was 68.26% and the total effective feeding rate was 49.14%. The effective feeding rate of caregivers of the grandparents' generation (59.07%) was higher than that of the caregivers of the parents' generation (45.08%) ( P<0.05). Logistic regression analysis suggested that, for caregivers of the parents' generation, information communication channel of village and township physicians (odds ratio [ OR]=2.20, 95% confidence interval [ CI]: 1.13-4.31) and communication messages on feeding methods ( OR=1.80, 95% CI: 1.19-2.73) and benefits of MNP ( OR=2.40, 95% CI: 1.61-3.57) facilitated their effective feeding behavior, while communication message concerning the free availability of MNP ( OR=0.58, 95% CI: 0.38-0.87) inhibited their effective feeding behavior. For caregivers of the grandparents' generation, information communication channel of village and township physicians ( OR=2.95, 95% CI: 1.12-7.76) and communication messages on the feeding methods ( OR=2.86, 95% CI: 1.34-6.09) were facilitating factors of their effective feeding behaviors. Conclusion: The main channel of MNP information delivered to caregivers from the areas covered by the study was face-to-face explanation by doctors. The message communicated mainly involved three aspects--the administration method, the benefits and free availability of MNP. The channel and message of MNP information communnication had different effects on the feeding behaviors of caregivers of the parents' and grandparents' generations. Future research should focus on developing targeted information communication strategies according to the characteristics of populations from different generations, so as to improve the caregivers' feeding behavior.

Naturally-Occurring Antibodies Against Bim are Decreased in Alzheimer's Disease and Attenuate AD-type Pathology in a Mouse Model.

Increased neuronal apoptosis is an important pathological feature of Alzheimer's disease (AD). The Bcl-2-interacting mediator of cell death (Bim) mediates amyloid-beta (Aß)-induced neuronal apoptosis. Naturally-occurring antibodies against Bim (NAbs-Bim) exist in human blood, with their levels and functions unknown in AD. In this study, we found that circulating NAbs-Bim were decreased in AD patients. Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions. Furthermore, NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated Aß deposition, tau hyperphosphorylation, microgliosis, and neuronal apoptosis in APP/PS1 mice. In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein. These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD.

Does the incorporation of strontium into calcium phosphate improve bone repair? A meta-analysis.

BACKGROUND: The application of calcium phosphate (CaP)-based bone substitutes plays an important role in periodontal regeneration, implant dentistry and alveolar bone reconstruction. The incorporation of strontium (Sr) into CaP-based bone substitutes appears to improve their biological properties, but the reported in vivo bone repair performance is inconsistent among studies. Herein, we conducted a systematic review and meta-analysis to investigate the in vivo performance of Sr-doped materials. METHODS: We searched PubMed, EMBASE (via OVIDSP), and reference lists to identify relevant animal studies. The search, study selection, and data extraction were performed independently by two investigators. Meta-analyses and sub-group analyses were conducted using Revman version 5.4.1. The heterogeneity between studies were assessed by I2. Publication bias was investigated through a funnel plot. RESULTS: Thirty-five studies were finally enrolled, of which 16 articles that reported on new bone formation (NBF) were included in the meta-analysis, covering 31 comparisons and 445 defects. The overall effect for NBF was 2.25 (95% CI 1.61-2.90, p < 0.00001, I2 = 80%). Eight comparisons from 6 studies reported the outcomes of bone volume/tissue volume (BV/TV), with an overall effect of 1.42 (95% CI 0.65-2.18, p = 0.0003, I2 = 75%). Fourteen comparisons reported on the material remaining (RM), with the overall effect being -2.26 (95% CI - 4.02 to - 0.50, p = 0.0009, I2 = 86%). CONCLUSIONS: Our study revealed that Sr-doped calcium phosphate bone substitutes improved in vivo performance of bone repair. However, more studies are also recommended to further verify this conclusion.

PKCα/ZFP64/CSF1 axis resets the tumor microenvironment and fuels anti-PD1 resistance in hepatocellular carcinoma.

BACKGROUND & AIMS: Despite remarkable advances in treatment, most patients with hepatocellular carcinoma (HCC) respond poorly to anti-programmed cell death 1 (anti-PD1) therapy. A deeper insight into the tolerance mechanism of HCC against this therapy is urgently needed. METHODS: We performed next-generation sequencing, multiplex immunofluorescence, and dual-color immunohistochemistry and constructed an orthotopic HCC xenograft tumor model to identify the key gene associated with anti-PD1 tolerance. A spontaneously tumorigenic transgenic mouse model, an in vitro coculture system, mass cytometry, and multiplex immunofluorescence were used to explore the biological function of zinc finger protein 64 (ZFP64) on tumor progression and immune escape. Molecular and biochemical strategies like RNA-sequencing, chromatin immunoprecipitation-sequencing and mass spectrometry were used to gain insight into the underlying mechanisms of ZFP64. RESULTS: We showed that ZFP64 is frequently upregulated in tumor tissues from patients with anti-PD1-resistant HCC. Elevated ZFP64 drives anti-PD1 resistance by shifting macrophage polarization toward an alternative activation phenotype (M2) and fostering an inhibitory tumor microenvironment. Mechanistically, we primarily demonstrated that protein kinase C alpha (PKCα) directly phosphorylates ZFP64 at S226, leading to its nuclear translocation and the transcriptional activation of macrophage colony-stimulating factor (CSF1). HCC-derived CSF1 transforms macrophages to the M2 phenotype to drive immune escape and anti-PD1 tolerance. Notably, Gö6976, a protein kinase inhibitor, and lenvatinib, a multi-kinase inhibitor, reset the tumor microenvironment and restore sensitivity to anti-PD1 by blocking the PKCα/ZFP64/CSF1 axis. CONCLUSIONS: We propose that the PKCα/ZFP64/CSF1 axis is critical for triggering immune evasion and anti-PD1 tolerance. Inhibiting this axis with Gö6976 or lenvatinib overcomes anti-PD1 resistance in HCC. LAY SUMMARY: Despite remarkable treatment progress, most patients with hepatocellular carcinoma respond poorly to anti-PD1 therapy (a type of immunotherapy). A deeper insight into the tolerance mechanisms to this therapy is urgently needed. Herein, we unravel a previously unexplored mechanism linking tumor progression, macrophage polarization, and anti-PD1 resistance, and offer an attractive novel target for anti-PD1 combination therapy, which may benefit patients with hepatocellular carcinoma.

Expression of cartilage oligomeric matrix protein (COMP) associates with capsular invasion in salivary gland pleomorphic adenoma.

BACKGROUND: Accumulating evidence shows that pleomorphic adenoma (PA) exhibits a unique capsular invasion and with a crucial role in recurrence. This study was designed to explore RNA expression profiles in salivary gland PA in an attempt to further analyse genes associate with capsule invasion. METHODS: We evaluated the expression profiles of 4 salivary gland PA patients by RNA-sequencing. The principal functions of the differentially expressed mRNAs (DEGs) were explored using GO and KEGG analysis. Then, RT-qPCR and correlation analyses were performed to verify the candidate DEGs in 59 PA patients, and immunohistochemical examinations were conducted to validate candidate DEGs. Finally, the COMP-related genes were screened using correlation and biological pathway enrichment analysis, and further validated by RT-qPCR. RESULTS: A total of 974 DEGs were significantly upregulated, and 1464 were downregulated (fold change ≥2.0; p < 0.05). Based on GO and KEGG analyses, extracellular matrix organization and the PI3K-Akt signalling pathway might play pivotal roles in the tumorigenesis of PA. 40 DEGs were screened and validated by RT-qPCR, 11 upregulated and 5 downregulated DEGs were consistent with the sequencing results. Cartilage oligomeric matrix protein (COMP) was identified to have a significant correlation with the capsular invasion of PA and expression of COMP in patients with invasive capsular PA was significantly stronger than PA. Finally, further results could reveal that 5 highest scoring genes were screened as hub genes for COMP. CONCLUSIONS: These findings suggested that COMP may be a prognostic target for PA and might contribute to its capsular invasion.

Hybrid sequencing reveals the full-length Nephila pilipes pyriform spidroin 1 (PySp1).

Araneid spider silk glands can spin seven silk types that have task-specific properties owing to the higher order structure of spider silk proteins. This gives silks superior potential as novel biomaterials. Nephila pilipes, the giant golden orb-weaver, is one of the largest spiders and spins silk with exceptional torsional deformation, toughness, and other properties to support its mass; further investigation relies on a complete amino acid sequence. However, there are no full-length N. pilipes spidroin sequences; in fact, across species, most sequences remain fragmentary because of repetitive region assembly difficulties in short-read sequencing. Here, we develop a hybrid sequencing method that utilizes short-read sequencing to identify seven spidroin terminals in N. pilipes, and long-read sequencing to confirm the full-length pyriform spidroin 1 (PySp1) gene. PySp1 is 11,181 base pairs, with a single exon encoding a 3,726 amino acid protein, the QQ(x)4Qx motif, and lower repeat homogenization, distinct characteristics of genera Nephilinae PySp1. The full-length N. pilipes PySp1 sequences sheds light on spidroin evolution and demonstrates a helpful strategy to find full-length spidroins.

Integrated analysis of transcriptomics to identify hub genes in primary Sjögren's syndrome.

OBJECTIVE: The treatment of patients with primary Sjögren's syndrome is a clinical challenge. Gene expression profile analysis and comprehensive network methods for complex diseases can provide insight into molecular characteristics in the clinical context. MATERIALS AND METHODS: We downloaded gene expression datasets from the Gene Expression Omnibus (GEO) database. We screened differentially expressed genes (DEG) between the pSS patients and the controls by the robust rank aggregation (RRA) method. We explored DEGs' potential function using gene function annotation and PPI network analysis. RESULTS: GSE23117, GSE40611, GSE80805, and GSE127952 were included, including 38 patients and 30 controls. The RRA integrated analysis determined 294 significant DEGs (241 upregulated and 53 downregulated), and the most significant gene aberrantly expressed in SS was CXCL9 (p = 6.39E-15), followed by CXCL13 (p = 1.53E-13). Immune response (GO:0006955; p = 4.29E-32) was the most significantly enriched biological process in GO (gene ontology) analysis. KEGG pathway enrichment analysis showed that cytokine-cytokine receptor interaction (hsa04060; p = 6.46E-10) and chemokine signaling pathway (hsa04062; p = 9.54E-09) were significantly enriched. We defined PTPRC, CD86, and LCP2 as the hub genes based on the PPI results. CONCLUSION: Our integrated analysis identified gene signatures and helped understand molecular changes in pSS.

Systematic review and Meta-analysis of efficacy and safety of Ningxinbao Capsules in treatment of arrhythmia / 中国中药杂志

To systematically evaluate the efficacy and safety of Ningxinbao Capsules in treatment of arrhythmia by Meta-analysis. Randomized controlled trial(RCT) or quasi-randomized control trial(Quasi-RCT) on Ningxinbao Capsules treating arrhythmia were obtained by computer-based retrieval in CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Cochrane Library and EMbase as well as manual retrieval, with time limit from database establishment to April 7, 2020. According to the inclusion and exclusion criteria of trials, all RCTs were screened and evaluated. Then the effective data were collected and RevMan 5.3 Meta-analysis software was used for analysis. Thirteen trials were included, involving 1 379 patients in total. Ningxinbao Capsules combined with anti-arrhythmia Western medicine were adopted as the intervention, and the patients in control group were treated with the anti-arrhythmia Western medicine alone. Meta-analysis results showed that as compared to control group, Ningxinbao Capsules combined with anti-arrhythmia Western medicine group was superior in clinical efficacy, dynamic electrocardiogram and average heart rate in patients with bradycardia, with indicated statistically significant differences. Ningxinbao Capsules had fewer adverse reactions and could relieve the toxic and side effects of anti-arrhythmia medicine possibly. The study showed that Ningxinbao Capsules played a role in treatment of arrhythmia and was relatively safe. However, due to the limited quality of the included studies, high-quality clinical trials are needed to verify the conclusions.