Comparison of safety and effectiveness of different sheaths in ablation of focal atrial tachycardia: a retrospective study.

Background: A novel visualized steerable sheath, referred to as the Vizigo sheath, has been utilized in clinical interventions. The objective of this study was to evaluate and contrast the efficacy and safety of the Vizigo sheath with other sheaths in the catheter ablation (CA) for focal atrial tachycardia (FAT). Methods: A retrospective cohort study was conducted on consecutive patients with CA for FAT from March 2019 to February 2022. Objectives were to assess the impact of the Vizigo sheath on acute and long-term ablation success rates, procedural and fluoroscopy times, and contact force (CF). Results: A total of 164 patients, mean age 50±15 years, 97 (59.1%) women, underwent CA of FAT using the Vizigo sheath (N=42), non-visualized steerable sheath (N=36), or other conventional sheath (N=86). Age, sex, body mass index (BMI), presence of hypertension, heart failure, and diabetes mellitus were not significantly different among the three groups. The acute success rate of 94.0% was similar among the three groups. Over a follow-up of 14±2 months, the Vizigo sheath was associated with superior arrhythmia-free survival (88.1%) when compared to non-visualized steerable (69.4%; P=0.04) and other conventional (72.1%, P=0.046) sheaths. Procedural duration, number of ablation lesions, and ablation times were similar among the three groups. However, the Vizigo sheath was associated with lower fluoroscopy times (e.g., 145 vs. 250 s with Vizigo versus non-visualized steerable sheaths, P=0.03) and higher CF (e.g., average CF 12.0 versus 8.0 g with Vizigo versus non-visualized steerable sheaths, P=0.003). Conclusions: The application of Vizigo sheath can improve the long-term success rate of FAT and reduce the radiation exposure of patients and medical staff in our single-center limited sample study. More research may be needed in the future to confirm our findings.

Are children with IgA nephropathy different from adult patients?

BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.

Physiological and molecular responses in phosphorus-hyperaccumulating Polygonum species to high phosphorus exposure.

Phosphorus (P)-hyperaccumulators for phytoextraction from P-polluted areas generally show rapid growth and accumulate large amounts of P without any toxicity symptom, which depends on a range of physiological processes and gene expression patterns that have never been explored. We investigated growth, leaf element concentrations, P fractions, photosynthetic traits, and leaf metabolome and transcriptome response in amphibious P-hyperaccumulators, Polygonum hydropiper and P. lapathifolium, to high-P exposure (5 mmol L-1), with 0.05 mmol L-1 as the control. Under high-P exposure, both species demonstrated good growth, allocating more P to metabolite P and inorganic P (Pi) accompanied by high potassium and calcium. The expression of a cluster of unigenes associated with photosynthesis was maintained or increased in P. lapathifolium, explaining the increase in net photosynthetic rate and the rapid growth under high-P exposure. Metabolites of trehalose metabolism, including trehalose 6-phosphate and trehalose, were sharply increased in both species by the high-P exposure, in line with the enhanced expression of associated unigenes, indicating that trehalose metabolic pathway was closely related to high-P tolerance. These findings elucidated the physiological and molecular responses involved in the photosynthesis and trehalose metabolism in P-hyperaccumulators to high-P exposure, and provides potential regulatory pathways to improve the P-phytoextraction capability.

Correlation Between the Clinicopathological Features of Papillary Thyroid Carcinoma Complicated with Hashimoto's Thyroiditis, BRAF V600E Gene Mutation, and RET Gene Rearrangement.

OBJECTIVE: To analyse the expression of BRAF V600E protein and RET gene rearrangement in papillary thyroid carcinoma (PTC) combined with Hashimoto's thyroiditis (HT) and to explore its clinical and pathological significance. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Pathology, East China Normal University (Wuhu No. 2 People's Hospital), Wuhu, China, from January 2019 to July 2022. METHODOLOGY: The study population of 150 patients who underwent central lymph node dissection. They were divided into two groups: the PTC group (76/150, 50.7%) and the PTC with HC group (74/150, 49.3%). The expression of BRAF V600E protein was detected using immunohistochemistry, and the RET gene rearrangement status was detected using fluorescence in situ hybridisation. The detection results and clinical pathological characteristics were statistically analysed. RESULTS: Compared with the PTC group, the prevalence rate of female PTC in HT group was significantly higher than that of the male group, the rate of lymph node metastasis was lower, and the proportion of tumour diameter ≤ 1cm was higher (p < 0.05). However, no significant difference in patient age and multifocality was found between the two groups (p > 0.05). The BRAF V600E positive rate in the PTC combined with HT group (48.6%) was lower than in the PTC group (73.7%), and the RET gene rearrangement positive rate was higher than in the PTC group (p < 0.05). The expression of BRAF V600E protein in PTC combined with HT is correlated with multifocality (p < 0.05), and there is a correlation between RET gene rearrangement and the gender of the patient in the PTC group (p < 0.05). CONCLUSION: There is a lower rate of BRAF V600E protein positivity in PTC combined with HT patients, as well as a higher rate of RET gene rearrangements positive in PTC combined with HT patients. There is a correlation between multifocality and BRAF V600E protein expression. KEY WORDS: Papillary thyroid carcinoma, Hashimoto's thyroiditis, BRAF V600E protein, RET gene rearrangement.

Peripheral nerve injury associated with JEV infection in high endemic regions, 2016-2020: a multicenter retrospective study in China.

ABSTRACTPreviously, we have reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016 to 2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

Activated non-neuronal cholinergic system correlates with non-type 2 inflammation and exacerbations in severe asthma.

BACKGROUND: Non-neuronal cholinergic system (NNCS) contributes to various inflammatory airway diseases. However, the role of NNCS in severe asthma (SA) remains largely unexplored. OBJECTIVE: To explore airway NNCS in SA. METHODS: In this prospective cohort study based on the Australasian Severe Asthma Network in a real-world setting, patients with SA (n=52) and non-SA (n=104) underwent clinical assessment and sputum induction. The mRNA levels of NNCS components and proinflammatory cytokines in sputum were detected using RT-qPCR, and the concentrations of acetylcholine (Ach)-related metabolites were examined using LC-MS/MS. Asthma exacerbations were prospectively investigated during the following 12 months. The association between NNCS and future asthma exacerbations was also analyzed. RESULTS: Patients with SA were less controlled and had worse airway obstruction, a lower bronchodilator response, higher doses of inhaled corticosteroids, and more add-on treatments. The sputum mRNA levels of NNCS components, such as muscarinic receptors M1R-M5R, OCT3, VACHT, and ACHE; proinflammatory cytokines; and Ach concentration in the SA group were significantly higher than those in the non-SA group. Furthermore, most NNCS components positively correlated with non-type (T) 2 inflammatory profiles, such as sputum neutrophils, IL8, and IL1B. In addition, the mRNA levels of sputum M2R, M3R, M4R, M5R, and VACHT were independently associated with an increased risk of moderate-to-severe asthma exacerbations. CONCLUSION: This study indicated that the NNCS was significantly activated in SA, leading to elevated Ach and was associated with clinical features, non-T2 inflammation, and future exacerbations of asthma, highlighting the potential role of the NNCS in the pathogenesis of SA.

Arginine Methylation of ß-Catenin Induced by PRMT2 Aggravates LPS-Induced Cognitive Dysfunction and Depression-Like Behaviors by Promoting Ferroptosis.

Depression is a prevalent and debilitating psychiatric disorder, imposing substantial societal and individual burdens. This study aims to investigate the involvement of ferroptosis and microglial polarization in the pathogenesis of depression, as well as the underlying mechanism. Increased protein arginine methyltransferase 2 (PRMT2) expression was observed in BV2 cells and the hippocampus following lipopolysaccharide (LPS) stimulation. Mechanistically, alkylation repair homolog protein 5 (ALKBH5)-mediated m6A modification enhanced the stability of PRMT2 mRNA. PRMT2 promoted arginine methylation of ß-catenin and induced proteasomal degradation of ß-catenin proteins, resulting in transcriptional inhibition of glutathione peroxidase 4 (GPX4). The upregulation of PRMT2 further accelerated microglia polarization by activating ferroptosis through the ß-catenin-GPX4 axis. Depletion of PRMT2 improved LPS-induced depressive- and anxiety-like behaviors as well as cognitive impairment by inhibiting ferroptosis and M1 polarization of microglia. Our findings underscore the crucial involvement of the ALKBH5-PRMT2-ß-catenin-GPX4 axis in ferroptosis and M1 polarization of microglia, thereby offering novel insights into the pathogenesis interventions for depression.

Heterogeneous engineering and carbon confinement strategy to synergistically boost the sodium storage performance of transition metal selenides.

Transition metal selenides (TMSs) stand out as a promising anode material for sodium-ion batteries (SIBs) owing to their natural resources and exceptional sodium storage capacity. Despite these advantages, their practical application faces challenges, such as poor electronic conductivity, sluggish reaction kinetics and severe agglomeration during electrochemical reactions, hindering their effective utilization. Herein, the dual-carbon-confined CoSe2/FeSe2@NC@C nanocubes with heterogeneous structure are synthesized using ZIF-67 as the template by ion exchange, resorcin-formaldehyde (RF) coating, and subsequent in situ carbonization and selenidation. The N-doped porous carbon promotes rapid electrolyte penetration and minimizes the agglomeration of active materials during charging and discharging, while the RF-derived carbon framework reduces the cycling stress and keeps the integrity of the material structure. More importantly, the built-in electric field at the heterogeneous boundary layer drives electron redistribution, optimizing the electronic structure and enhancing the reaction kinetics of the anode material. Based on this, the nanocubes of CoSe2/FeSe2@NC@C exhibits superb sodium storage performance, delivering a high discharge capacity of 512.6 mA h g-1 at 0.5 A g-1 after 150 cycles and giving a discharge capacity of 298.2 mA h g-1 at 10 A g-1 with a CE close to 100.0 % even after 1000 cycles. This study proposes a viable method to synthesize advanced anodes for SIBs by a synergy effect of heterogeneous interfacial engineering and a carbon confinement strategy.

Rapid Detection of Tannin Content in Wine Grapes Using Hyperspectral Technology.

Wine grape quality is influenced by the variety and growing environment, and the quality of the grapes has a significant impact on the quality of the wine. Tannins are a crucial indicator of wine grape quality, and, therefore, rapid and non-destructive methods for detecting tannin content are necessary. This study collected spectral data of Pinot Noir and Chardonnay using a geophysical spectrometer, with a focus on the 500-1800 nm spectrum. The spectra were preprocessed using Savitzky-Golay (SG), first-order differential (1D), standard normal transform (SNV), and their respective combinations. Characteristic bands were extracted through correlation analysis (PCC). Models such as partial least squares (PLS), support vector machine (SVM), random forest (RF), and one-dimensional neural network (1DCNN) were used to model tannin content. The study found that preprocessing the raw spectra improved the models' predictive capacity. The SVM-RF model was the most effective in predicting grape tannin content, with a test set R2 of 0.78, an RMSE of 0.31, and an RE of 10.71%. These results provide a theoretical basis for non-destructive testing of wine grape tannin content.

The effects of behavioral intervention on anthropometric, clinical, and biochemical parameters in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

Objective: To evaluate the effects of behavioral intervention for polycystic ovary syndrome (PCOS). Methods: Electronic databases were searched, including Pubmed, Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to 1 April 2023. Inclusion criteria for this study required a diagnosis of PCOS. Interventions of interest included behavioral intervention and routine treatment compared with routine treatment. The studies included in the analysis were designed as randomized controlled trials (RCTs). We conducted meta-analyses following the recommended guidelines. The data was analyzed using either the random effects model or fixed effects model. The results of the studies were expressed as either mean differences (MD) or standardized mean differences (SMD) along with their corresponding 95% confidence intervals (CIs). Results: Eight RCTs were identified, including data from 744 patients (415 in the intervention group and 329 in the control group). The results indicate an improvement in the effectiveness of behavioral interventions for weight loss (MD: -1.07; 95% CI: -2.1 to 0.03; I2 = 0%; P=0.04), body mass index (BMI) (MD: -1.12; 95% CI: -1.92 to -0.33; I2 = 73%; P=0.006), waist circumference (MD: -3.97; 95% CI: -5.64 to -2.29; I2 = 0%; P<0.00001), quality of life about weight (MD: 0.58; 95% CI: 0.15 to 1.02; I2 = 0%; P=0.008), depression (SMD: -1.12; 95% CI: -2.35 to -0.07; I2 = 92%; P=0.04), and triglycerides (MD: -0.16; 95% CI: -0.27 to -0.05; I2 = 27%; P=0.004). However, there were no significant differences in menstrual cycles, hirsutism, emotions, and infertility. The study also found that behavioral interventions had no significant effect on systolic and diastolic blood pressure, high-density lipoprotein, low-density lipoprotein, homeostasis model assessment of insulin resistance, testosterone, total cholesterol, fasting glucose, fasting insulin, hemoglobin A1C, and sex hormone binding globulin. Conclusion: Behavioral intervention supplementation contributes to weight loss, reduction in BMI and waist circumference, and improvement in depression among patients with PCOS. However, no significant improvement was observed in the biochemical index and quality of life. The long-term effects of behavioral intervention for PCOS remain unclear due to limitations in the quality of the studies involved and the short duration of treatment. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023442875.

Circadian Rhythms in Cardiovascular Metabolism.

Energetic demand and nutrient supply fluctuate as a function of time-of-day, in alignment with sleep-wake and fasting-feeding cycles. These daily rhythms are mirrored by 24-hour oscillations in numerous cardiovascular functional parameters, including blood pressure, heart rate, and myocardial contractility. It is, therefore, not surprising that metabolic processes also fluctuate over the course of the day, to ensure temporal needs for ATP, building blocks, and metabolism-based signaling molecules are met. What has become increasingly clear is that in addition to classic signal-response coupling (termed reactionary mechanisms), cardiovascular-relevant cells use autonomous circadian clocks to temporally orchestrate metabolic pathways in preparation for predicted stimuli/stresses (termed anticipatory mechanisms). Here, we review current knowledge regarding circadian regulation of metabolism, how metabolic rhythms are synchronized with cardiovascular function, and whether circadian misalignment/disruption of metabolic processes contribute toward the pathogenesis of cardiovascular disease.

Transcutaneous auricular vagus nerve stimulation with task-oriented training improves upper extremity function in patients with subacute stroke: a randomized clinical trial.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising brain stimulation modality in poststroke upper extremity rehabilitation. Although several studies have examined the safety and reliability of taVNS, the mechanisms underlying motor recovery in stroke patients remain unclear. Objectives: This study aimed to investigate the effects of taVNS paired with task-oriented training (TOT) on upper extremity function in patients with subacute stroke and explore the potential underlying mechanisms. Methods: In this double-blinded, randomized, controlled pilot trial, 40 patients with subacute stroke were randomly assigned to two groups: the VNS group (VG), receiving taVNS during TOT, and the Sham group (SG), receiving sham taVNS during TOT. The intervention was delivered 5 days per week for 4 weeks. Upper extremity function was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT). Activities of daily living were measured by the modified Barthel Index (MBI). Motor-evoked potentials (MEPs) were measured to evaluate cortical excitability. Assessments were administered at baseline and post-intervention. Additionally, the immediate effect of taVNS was detected using functional near-infrared spectroscopy (fNIRS) and heart rate variability (HRV) before intervention. Results: The VG showed significant improvements in upper extremity function (FMA-UE, ARAT) and activities of daily living (MBI) compared to the SG at post-intervention. Furthermore, the VG demonstrated a higher rate of elicited ipsilesional MEPs and a shorter latency of MEPs in the contralesional M1. In the VG, improvements in FMA-UE were significantly associated with reduced latency of contralesional MEPs. Additionally, fNIRS revealed increased activation in the contralesional prefrontal cortex and ipsilesional sensorimotor cortex in the VG in contrast to the SG. However, no significant between-group differences were found in HRV. Conclusion: The combination of taVNS with TOT effectively improves upper extremity function in patients with subacute stroke, potentially through modulating the bilateral cortex excitability to facilitate task-specific functional recovery.

Allometric Growth Pattern and Hunger Tolerance of Hemibarbus maculatus Bleeker Larvae.

To clarify the allometric growth pattern and hunger tolerance of Hemibarbus maculatus Bleeker larvae, the morphological lengths of their functional organs were measured continuously and their primary feeding rates under a state of starvation were studied. A control group and starvation group were set up for this study, and 10 larvae were sampled from each group every day in order to study their allometric growth pattern and starvation tolerance. The results indicated that the Hemibarbus maculatus larvae opened their mouths for feeding at 4 days after hatching, and that the yolk sac disappeared completely at 11 days after hatching. The Hemibarbus maculatus larvae preferentially developed their heads, fins, and eyes, related to the functions of feeding, balancing, and swimming, in order to cope with complex environments. The growth inflection points for the head length, pectoral fin length, dorsal fin length, eye diameter, eye spacing, snout length, and body height were characterized by total lengths of 10.93 mm, 11.67 mm, 11.67 mm, 13.17 mm, 16.53 mm, 15.13 mm, and 15.13 mm, respectively. Prior to and following the inflection point, positive allometric growth was observed in all organs. After the inflection point, the dorsal fin continued to maintain positive allometric growth, while the others changed to isometric allometric growth. A growth inflection point was not observed for trunk length or the lengths of the tail and anal fins. The trunk length always maintained negative allometry, while the tail and anal fin lengths were reversed. The growth inflection point of the tail length was at a total length of 13.68 mm. Before and after the growth inflection point, negative and isometric allometric growths were observed, respectively. According to the relationship between the total length and number of days after hatching, the growth inflection point of the Hemibarbus maculatus larvae was concentrated at TL = 10.93-16.53 mm, which was observed 14-20 days after hatching. The point of no return for the Hemibarbus maculatus larvae was 12-13 days after hatching, and the ratio of days after hatching in the mixed trophic period to the endotrophic period was 1.75, indicating that the larvae had strong hunger tolerance. Therefore, when considering a water temperature of 22.66 ± 1.56 °C, 4-5 days after hatching is the best time to cultivate in the pond, and it should not be carried out later than 12 days after hatching.

Two novel pathogenic variants in the TCOF1 found in two Chinese cases of Treacher Collins syndrome.

BACKGROUND: Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology. METHODS: The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing. RESULTS: Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before. CONCLUSION: Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.

Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis.

BACKGROUND: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. METHODS: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. RESULTS: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. CONCLUSIONS: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.

Transcriptomic Signature of 3D Hierarchical Porous Chip Enriched Exosomes for Early Detection and Progression Monitoring of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor, and the current non-invasive diagnosis method based on serum markers, such as α-fetoprotein (AFP), and des-γ-carboxy-prothrombin (DCP), has limited efficacy in detecting it. Therefore, there is a critical need to develop novel biomarkers for HCC. Recent studies have highlighted the potential of exosomes as biomarkers. To enhance exosome enrichment, a silicon dioxide (SiO2) microsphere-coated three-dimensional (3D) hierarchical porous chip, named a SiO2-chip is designed. The features of the chip, including its continuous porous 3D scaffold, large surface area, and nanopores between the SiO2 microspheres, synergistically improved the exosome capture efficiency. Exosomes from both non-HCC and HCC subjects are enriched using an SiO2-chip and performed RNA sequencing to identify HCC-related long non-coding RNAs (lncRNAs) in the exosomes. This study analysis reveales that LUCAT-1 and EGFR-AS-1 are two HCC-related lncRNAs. To further detect dual lncRNAs in exosomes, quantitative real time polymerase chain reaction (qRT-PCR) is employed. The integration of dual lncRNAs with AFP and DCP significantly improves the diagnostic accuracy. Furthermore, the integration of dual lncRNAs with DCP effectively monitors the prognosis of patients with HCC and detects disease progression. In this study, a liquid biopsy-based approach for noninvasive and reliable HCC detection is developed.

The Association between Abstinence Period and Semen Parameters in Humans: Results in Normal Samples and Different Sperm Pathology.

BACKGROUND: The impact of sexual abstinence on sperm quality, particularly in pathological cases, is a subject of debate. We investigated the link between abstinence duration and semen quality in both normal and pathological samples. METHODS: We analyzed semen samples from 4423 men undergoing fertility evaluation, comprising 1256 samples from healthy individuals and 3167 from those with conditions such as oligozoospermia, asthenozoospermia, teratozoospermia, or a combination of these factors, namely oligoasthenoteratozoospermia (OAT). Parameters including sperm concentration, the percentage of progressively motile spermatozoa, total motile sperm count, and the percentage of spermatozoa with normal morphology were assessed at various abstinence durations (each day, 0-2, 3-7, and >7 days). RESULTS: Extended abstinence correlated with higher sperm concentration overall (p < 0.001), except in oligozoospermia. Longer abstinence reduced progressive motility in normal (p < 0.001) and teratozoospermic samples (p < 0.001). Shorter abstinence was linked to higher morphologically normal sperm in normal samples (p = 0.03), while longer abstinence did so in oligoasthenoteratozoospermic samples (p = 0.013). CONCLUSION: The findings suggest that a prolonged abstinence time is linked to higher sperm concentration, while optimal sperm motility is observed after shorter abstinence periods. However, results regarding morphology remain inconclusive. Recommendations on abstinence duration should be tailored based on the specific parameter requiring the most significant improvement.

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE.

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.