Diagnostic value and clinical significance of lncRNA LINC01123 combined with fibrinogen in acute cerebral infarction.

OBJECTIVE: To explore the diagnostic value and clinical significance of lncRNA LINC01123 (LINC01123) binding fibrinogen in acute cerebral infarction (ACI) by evaluating the expression and potential molecular mechanism of LINC01123 in patients with acute cerebral infarction. METHODS: The clinical data of all the volunteers were collected. The level of serum LINC01123 in ACI patients was detected by RT-qPCR. The relationship between LINC01123 and fibrinogen was studied via Pearson's correlation analysis. ROC curve was used to evaluate the diagnostic value of LINC01123 and fibrinogen for ACI. The risk factors of ACI were investigated by Binary Logistic regression analysis. And the targeting relationship between LINC01123 and downstream miR-361-3p was verified through luciferase activity assay. RESULTS: Serum LINC01123 and fibrinogen levels were upregulated in ACI patients compared with healthy controls (P < 0.001), and there was a positive correlation between them (r = 0.6537, P < 0.001). In predicting the occurrence of ACI, LINC01123 and fibrinogen have high diagnostic value, and the AUC of combined diagnosis was 0.961, and the sensitivity and specificity (92.54%, 85.82%) were more significant. Meanwhile, LINC01123 and fibrinogen were confirmed to be independent risk factors for ACI (P < 0.0001). Mechanistically, miR-361-3p is the target of LINC01123. The expression of miR-361-3p was low in the serum of ACI patients, which was negatively correlated with the LINC01123 expression (r = -0.6885, P < 0.0001). CONCLUSION: LINC01123 combined with fibrinogen may have important reference value in the diagnosis of ACI as serum markers, which may become clinical indicators to predict the occurrence of ACI.

Integrated Network Pharmacology Analysis and Experimental Validation to Elucidate the Mechanism of Acteoside in Treating Diabetic Kidney Disease.

Background: Acteoside, an active ingredient found in various medicinal herbs, is effective in the treatment of diabetic kidney disease (DKD); however, the intrinsic pharmacological mechanism of action of acteoside in the treatment of DKD remains unclear. This study utilizes a combined approach of network pharmacology and experimental validation to investigate the potential molecular mechanism systematically. Methods: First, acteoside potential targets and DKD-associated targets were aggregated from public databases. Subsequently, utilizing protein-protein interaction (PPI) networks, alongside GO and KEGG pathway enrichment analyses, we established target-pathway networks to identify core potential therapeutic targets and pathways. Further, molecular docking facilitated the confirmation of interactions between acteoside and central targets. Finally, the conjectured molecular mechanisms of acteoside against DKD were verified through experimentation on unilateral nephrectomy combined with streptozotocin (STZ) rat model. The underlying downstream mechanisms were further investigated. Results: Network pharmacology identified 129 potential intersected targets of acteoside for DKD treatment, including targets such as AKT1, TNF, Casp3, MMP9, SRC, IGF1, EGFR, HRAS, CASP8, and MAPK8. Enrichment analyses indicated the PI3K-Akt, MAPK, Metabolic, and Relaxin signaling pathways could be involved in this therapeutic context. Molecular docking revealed high-affinity binding of acteoside to PIK3R1, AKT1, and NF-κB1. In vivo studies validated the therapeutic efficacy of acteoside, demonstrating reduced blood glucose levels, improved serum Scr and BUN levels, decreased 24-hour urinary total protein (P<0.05), alongside mitigated podocyte injury (P<0.05) and ameliorated renal pathological lesions. Furthermore, this finding indicates that acteoside inhibits the expression of pyroptosis markers NLRP3, Caspase-1, IL-1ß, and IL-18 through the modulation of the PI3K/AKT/NF-κB pathway. Conclusion: Acteoside demonstrates renoprotective effects in DKD by regulating the PI3K/AKT/NF-κB signaling pathway and alleviating pyroptosis. This study explores the pharmacological mechanism underlying acteoside's efficacy in DKD treatment, providing a foundation for further basic and clinical research.

Early detection of phlebitis among hematology-oncology patients: a best practice implementation project.

INTRODUCTION: Peripherally-inserted venous catheters (PIVC) are essential for cancer patients to receive treatment. Phlebitis is a major complication of PIVC. Currently, nurses' assessment of phlebitis mainly involves visual inspection. However, the latest literature suggests palpation for tenderness to promote the early detection of phlebitis. OBJECTIVES: This project evaluated the effectiveness of a bundle approach to increase nurses' compliance with PIVC site assessment to promote early detection of phlebitis (grade 2 and above). METHODS: The JBI Evidence Implementation Framework was used to conduct this project in a 28-bed hematology-oncology ward in a Singapore hospital. The bundle approach used in this project consisted of a training presentation, medical mannequin, and phlebitis scale card. The rate of nurses' compliance with best practice for PIVC site assessment was measured at 1 month and 6 months post-implementation. The incidence of phlebitis was monitored up until 12 months post-implementation. RESULTS: Baseline data indicated that only 18.75% (3 out of 16) nurses palpated for tenderness when assessing for phlebitis. Data at 1 month and 6 months post-implementation reported sustained high compliance rates of 85.71% (24 out of 28) and 89.29% (25 out of 28), respectively. Late detection of phlebitis was reduced by 66% (from three cases to one case) at 6 months post-implementation, and no patients required invasive interventions. CONCLUSIONS: The bundle approach used in this project facilitated early detection of phlebitis following the inclusion of palpation into nurses' assessment for phlebitis. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A204.

Establishment of a Multiplex Detection Method for Common Bacteria in Blood Based on Human Mannan-Binding Lectin Protein-Conjugated Magnetic Bead Enrichment Combined with Recombinase-Aided PCR Technology.

Objective: Recombinase-aided polymerase chain reaction (RAP) is a sensitive, single-tube, two-stage nucleic acid amplification method. This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), and Acinetobacter baumannii (AB) in the bloodstream based on recombinant human mannan-binding lectin protein (M1 protein)-conjugated magnetic bead (M1 bead) enrichment of pathogens combined with RAP. Methods: Recombinant plasmids were used to evaluate the assay sensitivity. Common blood influenza bacteria were used for the specific detection. Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR (M-RAP) and quantitative PCR (qPCR) assays. Kappa analysis was used to evaluate the consistency between the two assays. Results: The M-RAP method had sensitivity rates of 1, 10, and 1 copies/µL for the detection of SA, PA, and AB plasmids, respectively, without cross-reaction to other bacterial species. The M-RAP assay obtained results for < 10 CFU/mL pathogens in the blood within 4 h, with higher sensitivity than qPCR. M-RAP and qPCR for SA, PA, and AB yielded Kappa values of 0.839, 0.815, and 0.856, respectively ( P < 0.05). Conclusion: An M-RAP assay for SA, PA, and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

Long-Term Clinical Outcomes of Acute Kidney Disease in Patients Receiving Extracorporeal Membrane Oxygenation.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is widely used; however, studies on the long-term outcomes of ECMO are scarce. We investigated the long-term clinical outcomes of acute kidney disease (AKD) in patients receiving ECMO. METHODS: Electronic data (2009-2018) were retrospectively collected from a multicenter database. Patients were divided into two groups (AKD and non-AKD) according to their AKD status 8-90 days after the initiation of ECMO. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between the two groups. The primary outcomes were major adverse kidney events (MAKEs) and major adverse cardiovascular events (MACEs), and the secondary outcomes were all-cause readmission, sepsis-related readmission, infection-related readmission, and dementia. RESULTS: Total 395 patients were eligible for analysis; of them, 160 patients (40.5%) developed AKD. The AKD group had a higher risk of MAKEs (hazard ratio [HR]: 2.06; 95% confidence interval [CI]: 1.68-2.53) than did the non-AKD group. Subgroup analysis revealed that the observed unfavorable effect of AKD on the risk of MAKEs was more pronounced in patients receiving venovenous ECMO than in those receiving venoarterial ECMO (HR: 5.69 vs. 1.85, respectively; P for interaction = 0.004). AKD group had a higher risk of MACE during the initial 3-year post- ECMO in comparison to those without (HR: 1.68; 95% CI: 1.22-2.30). Moreover, the risks of all-cause, sepsis-related, and infection-related readmissions were high in AKD survivors. CONCLUSIONS: AKD is associated with an increased risk of long-term MAKEs and initial 3-year MACE in ECMO recipients. In addition, AKD is associated with increased risks of all-cause, infection-related, and sepsis-related readmissions.

Caregivers' Burden on Patients with Dementia Having Multiple Chronic Diseases.

Purpose: This study aimed to find the caregiving burden level for patients with dementia who had multiple chronic diseases by simultaneously considering both patient and caregiver factors. Participants and Methods: A cross-sectional study with 284 patients with dementia having multiple chronic diseases managed by the dementia collaborative care team at Changhua Christian Hospital in Taiwan was conducted. The input variables were from patients, such as age, gender, mood symptoms, and behavioral and psychological symptoms, and caregivers, including age, relation to the patient, caregiver's mood, and caregiving burden. The Apriori algorithm was employed to determine the association between patient and caregiver factors and different caregiving burden levels by setting up the minimum support of 1% and confidence of 90% along with lift >1. Results: When caring for patients with dementia, twenty scenarios were found for caregivers with a severe burden. In addition, 1936 scenarios were related to caregivers with a moderate-to-severe burden. Specifically, there were eight scenarios for patients with three chronic diseases which could be further categorized into five general rules. Two hundred and fifty scenarios belonging to patients with two chronic diseases could be classified into 16 different combinations from eight chronic diseases of the database. Conclusion: Caregiver's mood, patients with mild dementia, and patients aged 75-84 years were associated with a severe caregiving burden. College and above education of the caregiver, the patient aged 85 years or more, and at least one of caregiver's moods were the variables to result in a moderate-to-severe burden for caregivers caring for patients with three multiple chronic diseases. Moreover, college and above education of the caregiver, mood symptom, age of the caregiver, and age of the patient were important variables for caregivers who had a moderate-to-severe burden taking care of patients with two chronic diseases.

Dissociated contributions of working memory and inhibitory control to children's and adults' analogical reasoning: Analogical strategies matter.

This study investigated whether and how each component of working memory (WM) and inhibitory control (IC) is related to analogical reasoning. Specifically, the mediating roles of analogical strategies were examined and compared across children and adults. In total, 79 children (50 girls; M ± SD = 8.43 ± 0.59 years old) and 77 adults (35 female; 19.44 ± 0.82 years old) were administered tests of WM, IC, and analogical reasoning. In addition, participants' eye movement data during the analogical reasoning task were collected to classify the analogical strategies. The results showed that the semantic-constraint strategy completely mediated the relationship between WM (rather than IC) and analogical reasoning for children. However, for adults, the project-first strategy partially mediated the association between IC (rather than WM) and analogical reasoning. These findings reveal the dissociated roles of WM and IC in analogical reasoning through analogical strategies for children and adults and highlight the importance of analogical strategies.

Generation and characterization of monoclonal antibodies against pathologically phosphorylated TDP-43.

Inclusions containing TAR DNA binding protein 43 (TDP-43) are a pathological hallmark of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). One of the disease-specific features of TDP-43 inclusions is the aberrant phosphorylation of TDP-43 at serines 409/410 (pS409/410). Here, we developed rabbit monoclonal antibodies (mAbs) that specifically detect pS409/410-TDP-43 in multiple model systems and FTD/ALS patient samples. Specifically, we identified three mAbs (26H10, 2E9 and 23A1) from spleen B cell clones that exhibit high specificity and sensitivity to pS409/410-TDP-43 peptides in an ELISA assay. Biochemical analyses revealed that pS409/410 of recombinant TDP-43 and of exogenous 25 kDa TDP-43 C-terminal fragments in cultured HEK293T cells are detected by all three mAbs. Moreover, the mAbs detect pS409/410-positive TDP-43 inclusions in the brains of FTD/ALS patients and mouse models of TDP-43 proteinopathy by immunohistochemistry. Our findings indicate that these mAbs are a valuable resource for investigating TDP-43 pathology both in vitro and in vivo.

The association between gray matter volume in the hippocampal subfield and antidepressant efficacy mediated by abnormal dynamic functional connectivity.

An abnormality of structures and functions in the hippocampus may have a key role in the pathophysiology of major depressive disorder (MDD). However, it is unclear whether structure factors of the hippocampus effectively impact antidepressant responses by hippocampal functional activity in MDD patients. We collected longitudinal data from 36 MDD patients before and after a 3-month course of antidepressant pharmacotherapy. Additionally, we obtained baseline data from 43 healthy controls matched for sex and age. Using resting-state functional magnetic resonance imaging (rs-fMRI), we estimated the dynamic functional connectivity (dFC) of the hippocampal subregions using a sliding-window method. The gray matter volume was calculated using voxel-based morphometry (VBM). The results indicated that patients with MDD exhibited significantly lower dFC of the left rostral hippocampus (rHipp.L) with the right precentral gyrus, left superior temporal gyrus and left postcentral gyrus compared to healthy controls at baseline. In MDD patients, the dFC of the rHipp.L with right precentral gyrus at baseline was correlated with both the rHipp.L volume and HAMD remission rate, and also mediated the effects of the rHipp.L volume on antidepressant performance. Our findings suggested that the interaction between hippocampal structure and functional activity might affect antidepressant performance, which provided a novel insight into the hippocampus-related neurobiological mechanism of MDD.

Engineering of the AAV-Compatible Hair Cell-Specific Small-Size Myo15 Promoter for Gene Therapy in the Inner Ear.

Adeno-associated virus (AAV)-mediated gene therapy is widely applied to treat numerous hereditary diseases in animal models and humans. The specific expression of AAV-delivered transgenes driven by cell type-specific promoters should further increase the safety of gene therapy. However, current methods for screening cell type-specific promoters are labor-intensive and time-consuming. Herein, we designed a "multiple vectors in one AAV" strategy for promoter construction in vivo. Through this strategy, we truncated a native promoter for Myo15 expression in hair cells (HCs) in the inner ear, from 1,611 bp down to 1,157 bp, and further down to 956 bp. Under the control of these 2 promoters, green fluorescent protein packaged in AAV-PHP.eB was exclusively expressed in the HCs. The transcription initiation ability of the 2 promoters was further verified by intein-mediated otoferlin recombination in a dual-AAV therapeutic system. Driven by these 2 promoters, human otoferlin was selectively expressed in HCs, resulting in the restoration of hearing in treated Otof -/- mice for at least 52 weeks. In summary, we developed an efficient screening strategy for cell type-specific promoter engineering and created 2 truncated Myo15 promoters that not only restored hereditary deafness in animal models but also show great potential for treating human patients in future.

Safety and efficacy of transcatheter arterial embolization in autosomal dominant polycystic kidney patients with gross hematuria: Six case reports.

BACKGROUND: To retrospectively report the safety and efficacy of renal transcatheter arterial embolization for treating autosomal dominant polycystic kidney disease (ADPKD) patients with gross hematuria. CASE SUMMARY: The purpose of this study is to retrospectively report the safety and efficacy of renal transcatheter arterial embolization for treating ADPKD patients with gross hematuria. Materials and methods: During the period from January 2018 to December 2019, renal transcatheter arterial embolization was carried out on 6 patients with polycystic kidneys and gross hematuria. Renal arteriography was performed first, and then we determined the location of the hemorrhage and performed embolization under digital subtraction angiography monitoring. Improvements in routine blood test results, routine urine test results, urine color and postoperative reactions were observed and analyzed. Results: Renal transcatheter arterial embolization was successfully conducted in 6 patients. The indices of 5 patients and the color of gross hematuria improved after surgery compared with before surgery. No severe complication reactions occurred. CONCLUSION: For autosomal dominant polycystic kidney syndrome patients with gross hematuria, transcatheter arterial embolization was safe and effective.

Relationship between leaf vein traits of three dominant Quercus species and ecological factors in the Qinling Mountains, China.

We investigated the inter- and intra-species differences of leaf vein traits of three dominant Quercus species, Q. wutaishanica, Q. aliena var. acutiserrata, and Q. variabilis of Niubeiling (subtropical humid climate) and Taohuagou (warm temperate semi-humid climate), located in the eastern and western Qinling Mountains. The nine examined leaf vein traits included primary leaf vein width, secondary leaf vein width, mean fine vein width, primary vein density, fine vein density, vein areole diameter, areole density, 3D fine vein surface area, and fine vein volume. We further elucidated the influencing mechanisms and regulatory pathways of biotic and abiotic factors on leaf vein traits. The results showed that species identity had significant effects on eight out of nine leaf vein traits except 3D fine vein surface area, while habitat had significant effects on primary leaf vein width, secondary leaf vein width, vein areole diameter, fine vein density, and areole density. Altitude had significant effects on primary vein density, mean fine vein width, vein areole diameter, fine vein density and areole density. Habitat, tree species identity, and altitude had significantly interactive effects on primary leaf vein density, 3D fine vein surface area, and fine vein volume. There were significant differences in primary leaf vein width, mean fine vein width, areole density, 3D fine vein surface area, fine vein volume, primary vein density of Q. wutaishanica between the two studied habitats, but the differences were only found in secondary leaf vein width and areole density of Q. aliena var. acutiserrata and Q. variabilis. The examined leaf vein traits were influenced both by biotic and abiotic factors, with varying effect sizes. Among the biotic factors, petiole length, leaf length and width ratio had strong effect on leaf vein traits. Among the abiotic factors, climatic and soil factors had high effect size on vein traits, with the former being higher than the latter. Leaf vein traits were affected directly by biotic factors, but indirectly by abiotic factors (soil and climatic factors) via regulating biotic factors (leaf stoichiometry and leaf phenotypic traits).

Deep learning assists detection of esophageal cancer and precursor lesions in a prospective, randomized controlled study.

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.

Representativeness of the PIONEER-HF and PARAGLIDE-HF in patients hospitalized with acute heart failure.

AIMS: The PIONEER-HF and PARAGLIDE-HF trials aimed to determine the efficacy and safety of the in-hospital initiation of sacubitril/valsartan in patients hospitalized for AHF. However, whether the inclusion and exclusion criteria of the trials apply to patients encountered in real-world routine care is unclear. This study aimed to investigate the applicability of the PIONEER-HF and PARAGLIDE-HF trials to real-world AHF patients. METHODS AND RESULTS: We identified 28 293 AHF hospitalized patients between August 2008 to August 2017 from the Chang Gung Research Database and classified them into four groups based on left ventricular ejection fraction (LVEF) and trial criteria. Cox proportional hazards models were used to compare the risk of HF hospitalization and cardiovascular (CV) death. We defined PIONEER-HF eligible (n = 3683) and non-eligible (n = 3502) patients with an LVEF ≤40%, and PARAGLIDE-HF eligible (n = 5191) and non-eligible (n = 5832) patients with an LVEF >40%. Over a mean follow-up of 3.5 years, the PIONEER-HF non-eligible and eligible groups exhibited similar rates of HF hospitalization and CV death (41.1% vs. 41.8%, adjusted hazard ratio [aHR]: 0.95; 95% CI: 0.88-1.04). No significant difference was found in the composite outcome between PARAGLIDE-HF non-eligible and eligible groups (36.7% vs. 38.6%; aHR: 0.97; 95% CI: 0.90-1.04). CONCLUSIONS: Using trial criteria, only 31.3% of AHF patients were eligible for sacubitril-valsartan. Yet, non-eligible patients demonstrated similar outcomes to eligible patients, indicating a need for further evaluation of sacubitril-valsartan benefits in non-eligible AHF patients.

Relationship between the microenvironment and survival in kidney transplantation: a bibliometric analysis from 2013 to 2023.

Background: Kidney transplantation is considered the most effective treatment for end-stage renal failure. Recent studies have shown that the significance of the immune microenvironment after kidney transplantation in determining prognosis of patients. Therefore, this study aimed to conduct a bibliometric analysis to provide an overview of the knowledge structure and research trends regarding the immune microenvironment and survival in kidney transplantation. Methods: Our search included relevant publications from 2013 to 2023 retrieved from the Web of Science core repository and finally included 865 articles. To perform the bibliometric analysis, we utilized tools such as VOSviewer, CiteSpace, and the R package "bibliometrix". The analysis focused on various aspects, including country, author, year, topic, reference, and keyword clustering. Results: Based on the inclusion criteria, a total of 865 articles were found, with a trend of steady increase. China and the United States were the countries with the most publications. Nanjing Medical University was the most productive institution. High-frequency keywords were clustered into 6 areas, including kidney transplantation, transforming growth factor ß, macrophage, antibody-mediated rejection, necrosis factor alpha, and dysfunction. Antibody mediated rejection (2019-2023) was the main area of research in recent years. Conclusion: This groundbreaking bibliometric study comprehensively summarizes the research trends and advances related to the immune microenvironment and survival after kidney transplantation. It identifies recent frontiers of research and highlights promising directions for future studies, potentially offering fresh perspectives to scholars in the field.

Inhibiting Peptidoglycan Hydrolase Alleviates MRSA Pneumonia Through Autolysin-Mediated MDP-NOD2 Pathway.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a cause of staph infection that is difficult to treat because of resistance to some antibiotics. A recent study indicated that diarylurea ZJ-2 is a novel antibacterial agent against multi-drug resistant Enterococcus faecium. In this work, we refined the bactericidal mechanism of ZJ-2 as a peptidoglycan (PG) hydrolase by affecting AtlA-mediated PG homeostasis. Methods: A wild-type strain (WT) and a mutant strain (ΔatlA) were used to investigate the effects of ZJ-2 on the cell wall, PG, and autolysin regulatory system by antimicrobial susceptibility testing, hemolytic toxin assay, microanalysis, autolysis assay, qRT-PCR, ELISA and mouse model of pneumonia. Results: The results revealed that ZJ-2 down-regulated the expression of genes related to peptidoglycan hydrolase (PGH) (sprX, walR, atlA, and lytM), and reduced the levels of PG, muramyl dipeptide (MDP), cytokines, and hemolytic toxin, while ΔatlA interfered with the genes regulation and PG homeostasis. In the mouse MRSA pneumonia model, the same trend was observed in the nucleotide oligomerization domain protein 2 (NOD2) and relative proinflammatory factors. Conclusion: ZJ-2 may act as a novel inhibitor of PG hydrolyse, disrupting autolysin-mediated PG homeostasis, and reducing inflammation by down-regulating the MDP-NOD2 pathway.

Efficacy of catheter ablation in ganglionated plexus for malignant vasovagal syncope children.

AIM: Malignant vasovagal syncope in children seriously affects their physical and mental health. Our study aimed to explore the efficacy of catheter ablation in ganglionated plexus with malignant vasovagal syncope children. CONCLUSION: Catheter ablation of ganglionated plexus was safe and effective in children with malignant vasovagal syncope and can be used as a treatment option for these children. METHODS: A total of 20 children diagnosed with malignant vasovagal syncope were enrolled in Beijing Children's Hospital, affiliated with Capital Medical University. All underwent catheter ablation treatment of ganglionated plexus. Ganglionated plexuses of the left atrium were identified by high-frequency stimulation and/or anatomic landmarks being targeted by radiofrequency catheter ablation. The efficacy of the treatment was evaluated by comparing the remission rate of post-operative syncopal symptoms and the rate of negative head-up tilt results. Safety and adverse events were evaluated. RESULTS: After follow-up for 2.5 (0.6-5) years, the syncope symptom scores were decreased significantly compared with before treatment [3 (2-4) versus 5 (3-8) scores, P < 0.01]. Eighty-five per cent (17/20) children no longer experienced syncope, whilst 80% (16/20) children showed negative head-up tilt test after treatment. No adverse effects such as cardiac arrhythmia occurred in the children.

Integration of pathologic characteristics, genetic risk and lifestyle exposure for colorectal cancer survival assessment.

The development of an effective survival prediction tool is key for reducing colorectal cancer mortality. Here, we apply a three-stage study to devise a polygenic prognostic score (PPS) for stratifying colorectal cancer overall survival. Leveraging two cohorts of 3703 patients, we first perform a genome-wide survival association analysis to develop eight candidate PPSs. Further using an independent cohort with 470 patients, we identify the 287 variants-derived PPS (i.e., PPS287) achieving an optimal prediction performance [hazard ratio (HR) per SD = 1.99, P = 1.76 × 10-8], accompanied by additional tests in two external cohorts, with HRs per SD of 1.90 (P = 3.21 × 10-14; 543 patients) and 1.80 (P = 1.11 × 10-9; 713 patients). Notably, the detrimental impact of pathologic characteristics and genetic risk could be attenuated by a healthy lifestyle, yielding a 7.62% improvement in the 5-year overall survival rate. Therefore, our findings demonstrate the integrated contribution of pathologic characteristics, germline variants, and lifestyle exposure to the prognosis of colorectal cancer patients.

A Multiplex Recombinase-Aided qPCR Assay for Highly Sensitive and Rapid Detection of khe, blaKPC -2, and blaNDM -1 Genes in Klebsiella pneumoniae.

OBJECTIVE: This study aimed to establish a highly sensitive and rapid single-tube, two-stage, multiplex recombinase-aided qPCR (mRAP) assay to specifically detect the khe, blaKPC-2, and blaNDM-1 genes in Klebsiella pneumoniae. METHODS: mRAP was carried out in a qPCR instrument within 1 h. The analytical sensitivities of mRAP for khe, blaKPC-2, and blaNDM-1 genes were tested using recombinant plasmids and dilutions of reference strains. A total of 137 clinical isolates and 86 sputum samples were used to validate the clinical performance of mRAP. RESULTS: mRAP achieved the sensitivities of 10, 8, and 14 copies/reaction for khe, blaKPC-2, and blaNDM-1 genes, respectively, superior to qPCR. The Kappa value of qPCR and mRAP for detecting khe, blaKPC-2, and blaNDM-1 genes was 1, 0.855, and 1, respectively (p < 0.05). CONCLUSION: mRAP is a rapid and highly sensitive assay for potential clinical identification of khe, blaKPC-2, and blaNDM-1 genes in K. pneumoniae.

Syphilis and cardiovascular risk: a Taiwanese registry.

BACKGROUND AND AIMS: Studies on the impact of syphilis on the cardiovascular system in large populations are limited. This study investigated the effects of syphilis on cardiovascular outcomes. METHODS: Medical records from 2010 to 2015 were retrieved from the Taiwan National Health Insurance Research Database, linked to the Notifiable Infectious Diseases database from the Taiwan Centers for Disease Control. Patients with syphilis were identified, excluding those with missing information, under 20 years of age, or with a history of human immunodeficiency virus infection, acute myocardial infarction, heart failure, aortic regurgitation, replacement of the aortic valve, aneurysm and/or dissection of the aorta, atrial fibrillation, ischaemic stroke, haemorrhagic stroke, and venous thromboembolism. Primary outcomes included new-onset acute myocardial infarction, heart failure, aortic regurgitation, aneurysm and dissection of the aorta, atrial fibrillation, ischaemic stroke, haemorrhagic stroke, venous thromboembolism, cardiovascular death, and all-cause mortality. RESULTS: A total of 28 796 patients with syphilis were identified from 2010 to 2015. After exclusions and frequency matching, 20 601 syphilis patients and 20 601 non-syphilis patients were analysed. The relative rate (RR) was utilized in the analysis, as the competing risk of death was not considered. Compared with patients without syphilis, patients with syphilis had increased risks of acute myocardial infarction (RR 38%, 95% confidence interval [CI] 1.19-1.60, P < .001), heart failure (RR 88%, 95% CI 1.64-2.14, P < .001), aortic regurgitation (RR 81%, 95% CI 1.18-2.75, P = .006), atrial fibrillation (RR 45%, 95% CI 1.20-1.76, P < .001), ischaemic stroke (RR 68%, 95% CI 1.52-1.87, P < .001), haemorrhagic stroke (RR 114%, 95% CI 1.74-2.64, P < .001), venous thromboembolism (RR 67%, 95% CI 1.23-2.26, P = .001), cardiovascular death (RR 155%, 95% CI 2.11-3.08, P < .001), and all-cause death (RR 196%, 95% CI 2.74-3.19, P < .001) but not for aneurysm and dissection of the aorta. CONCLUSIONS: This study demonstrates that patients with syphilis have a higher risk of cardiovascular events and all-cause mortality compared with those without syphilis.