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Background & Aims: This study aimed to evaluate the feasibility of vonoprazan–minocycline (VM) dual therapy for Helicobacter pylori infection. Methods: In this open-label RCT, 120 H. pylori-infected patients (60 treatment-naïve and 60 treatment-failure cases) were randomized to receive vonoprazan–amoxicillin dual therapy (VA: vonoprazan 20 mg b.i.d. + amoxicillin 1.0 g t.i.d., control group) or VM dual therapy (vonoprazan 20 mg b.i.d. + minocycline 100 mg b.i.d., test group) for 14 days. The primary outcome was eradication rates. Secondary outcomes included adverse effects (AEs). Results: As first-line treatment, eradication rates were 96.7% (VA) vs. 90.0% (VM) in intention-to-treat (ITT) analysis (p = 0.30) and 96.7% (VA) vs. 96.4% (VM) in per-protocol (PP) analysis (p = 0.96). For rescue treatment, eradication rates were 86.7% (VA) vs. 76.7% (VM) in ITT (p = 0.32) and 89.7% (VA) vs. 79.3% (VM) in PP (p = 0.28). Overall eradication rates were 91.7% (VA) vs. 83.3% (VM) in ITT (p = 0.17) and 93.2% (VA) vs. 87.7% (VM) in PP (p = 0.31). VM had a higher incidence of AEs than VA (30.0% vs. 10.0%, p = 0.006), with dizziness being the most common (18.3%). Conclusions: VM dual therapy was shown to be an effective and safe treatment option, demonstrating comparable eradication rates to VA dual therapy. While VM had a slightly higher incidence of AEs, they were generally mild and manageable. VM remained a valuable alternative for patients with penicillin allergies or amoxicillin resistance.

Background and aimsThis study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for Helicobacter pylori infection in patients with penicillin allergy.MethodsIn this randomised controlled trial, treatment-naïve adults with H. pylori infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects.Results300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI −4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modified intention-to-treat analysis (difference 1.5%; 95% CI −4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI −2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010).ConclusionsVT dual therapy demonstrated efficacy and safety as a first-line treatment for H. pylori infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT.Trial registration numberChiCTR2300074693.

Previous studies tracking AMPA receptor (AMPAR) diffusion at synapses observed a large mobile extrasynaptic AMPAR pool. Using super-resolution microscopy, we examined how fluorophore size and photostability affected AMPAR trafficking outside of, and within, post-synaptic densities (PSDs) from rats. Organic fluorescent dyes (≈4 nm), quantum dots, either small (≈10 nm diameter; sQDs) or big (>20 nm; bQDs), were coupled to AMPARs via different-sized linkers. We find that >90% of AMPARs labeled with fluorescent dyes or sQDs were diffusing in confined nanodomains in PSDs, which were stable for 15 min or longer. Less than 10% of sQD-AMPARs were extrasynaptic and highly mobile. In contrast, 5–10% of bQD-AMPARs were in PSDs and 90–95% were extrasynaptic as previously observed. Contrary to the hypothesis that AMPAR entry is limited by the occupancy of open PSD ‘slots’, our findings suggest that AMPARs rapidly enter stable ‘nanodomains’ in PSDs with lifetime >15 min, and do not accumulate in extrasynaptic membranes. Forgetting is a common experience in our everyday life. Yet much remains unknown about how we remember, and about why our memories sometimes fail us. The brain contains 80 to 100 billion nerve cells or neurons, which communicate with one another at junctions called synapses. At a synapse, one neuron releases a chemical message, which must diffuse across a small gap, and then activate proteins called receptors on another neuron. If the first neuron activates the second repeatedly, the second cell responds by inserting additional receptors into its membrane at the synapse. This strengthens the connection between the two neurons. Strengthening of synapses is thought to be one of the key mechanisms underlying learning. To confirm this, it would be helpful to be able to monitor the movement and position of individual receptors at synapses. However, the space between the two nerve cells at at synapse, called the synaptic cleft, is no more than 40 nanometers wide. This is about 25 times thinner than a human hair, and too small to be seen with light microscopy. Electron microscopy can visualize synapses, but does not work in living tissue. The only other option is to attach a fluorescent label – either a dye or a man-made crystal called a quantum dot – to a protein found in synapses and monitor the resulting fluorescence. Though the probe must be small enough to pass through the synaptic cleft to do this. Using fluorescence microscopy, researchers have examined the distribution in synapses of proteins called AMPA receptors, which have a key role in memory. Multiple studies have shown groups of AMPA receptors gathered outside synapses. This has led to the suggestion that during learning, AMPA receptors wait outside the synapse until a space becomes available within the synapse’s membrane. However, this has yet to be confirmed directly, in part because conventional fluorescent dyes and quantum dots are too bulky to enter synaptic clefts when bound to a receptor. Lee et al. have now developed a quantum dot that is only 10 nanometers wide and therefore small enough to enter the synaptic cleft with an AMPA receptor attached. These small quantum dots were then used to label AMPA receptors in neurons collected from rats and then grown in a petri dish, which provided a completely new view of synapses. The images show that the majority of AMPA receptors in neurons circulate within confined domains – a little like holding pens – inside the synapse, rather than waiting outside as previously assumed. Labeling the receptors with smaller 4-nanometer-wide fluorescent tags produces a similar picture. Further work is still need to determine how AMPA receptors get into the synapse and contribute to new memories.

Hearing loss (HL) is a common sensorineural defect. Wide-spread genetic screening is important for early diagnosis and intervention. We aimed to evaluate and compare the clinical performance of the MeltPro HL assay and a targeted next-generation sequencing assay for genetic screening of HL and to explore the relationship between the c.109G > A genotype and the HL phenotype. From December 2021 to December 2022, we recruited 220 patients who agreed to undergo the MeltPro HL and targeted next-generation sequencing assays for genetic HL screening. In our cohort, the degree of HL was mainly mild to moderate (78.64%, 173/220). In the MeltPro HL and targeted next-generation sequencing genetic screening assays, 34 patients (34/220, 15.45%) and 145 patients (145/220, 65.91%), respectively, were genetic positive for variants in HL-related genes. GJB2 and SLC26A4 were the two most common HL-causing genes detected among our cohorts of outpatients in Xiamen. The most prevalent variants of GJB2 and SLC26A4 were c.109G > A and c.919–2 A > G, with allelic frequencies of 52.95% (233/440) and 2.50% (11/440), respectively. In addition, a biallelic c.109G > A variant was identified in 115 (79.31%, 115/145) patients, and 93.91% (108/115) of them had mild-to-moderate HL. Our data showed that the MeltPro HL assay is an easy-to-use, satisfactory, and cost-effective genetic screening method for routine use in most laboratories, especially in remote areas of China. It has great potential to improve the diagnosis and prevention of HL in Xiamen when variant c.109G > A is included.

Endoscopic antireflux therapy is widely used in clinical practice. Peroral endoscopic cardial constriction (PECC), antireflux mucosal intervention (ARMI), and radiofrequency ablation (RF) possess analogous antireflux mechanisms. This comprehensive systematic review and meta-analysis aimed to evaluate and compare the safety and effectiveness of antireflux therapy during endoscopic cardia peripheral tissue scar formation (ECSF) procedures. We comprehensively searched the Web of Science, PubMed, Embase, China National Knowledge Infrastructure, and Wan-Fang databases for articles published from January 1990 to January 2024. Network meta-analysis (NMA) was used to assess the outcomes, with outcome metrics including the Gastroesophageal Reflux Questionnaire (GERD-Q) score, proton pump inhibitor discontinuation rate, pH <4.2 percent acid reflux time (AET), lower esophageal pressure (LES pressure), DeMeester score, adverse events, and patient satisfaction. Twenty studies involving 1219 patients were included. PECC was significantly superior to RF in lowering the patients’ postoperative GERD-Q scores(MD = -2.34, 95% confidence interval (CI): [-3.02, -1.66]), augmentation of LES pressures(MD = 3.22, 95% CI: [1.21, 5.23]), and having a lower incidence of serious adverse events. ARMI was preferable to PECC (MD = -2.87, 95% CI [-4.23, -1.51])and RF (MD = -1.12, 95% CI [-1.79, -0.54]) in reducing the AET percentage, but was not as effective as PECC in lowering GERD-Q scores(MD = -1.50, 95% CI [-2.47, -0.53]). The incidence of adverse effects was less than 10% for all interventions, with most of them mildly self-resolving. Each ECSF procedure resulted in a favorable outcome in patients with GERD. Considering the safety and efficacy of treatment, PECC was the most favorable choice among ECSF procedures.

Esophagogastroduodenoscopy (EGD) serves as a standard screening modality for upper gastrointestinal (GI) tumors, though standardized quality metrics remain undefined. Crucially, there was little direct evidence previously demonstrating the impact of the number of images taken during EGD on the detection rates of early upper gastrointestinal cancer (UGIC). This multicenter retrospective study aimed to assess the influence of the number of photographic images on early UGIC detection rates and identify associated risk factors. We retrospectively analyzed the data of 245,161 subjects who underwent EGD either as part of a health screening program or as symptomatic patients at Zhejiang Provincial Hospital of Traditional Chinese Medicine and Zhejiang Provincial People’s Hospital between May 2018 and October 2024. Cases were stratified by image count: < 20 (low), 20–40 (medium), and > 40 (high). Early UGIC was histologically confirmed. Primary outcomes were the comparison of detection rates across groups; secondary outcomes involved identifying detection-associated factors via logistic regression. Early UGIC detection rates were significantly higher in the high-image group versus the low and medium groups ( p  < 0.05). Subanalysis revealed optimal detection with > 80 images. Endoscopist-specific detection rates correlated strongly with image count ( p  < 0.001). Multivariate analysis identified increased image acquisition (OR 1.32, 95% CI 1.18–1.47), advanced age (OR 2.14, 95% CI 1.89–2.42), and male sex (OR 1.48, 95% CI 1.32–1.65) as independent predictors of early UGIC detection. The number of photographic images taken during EGD was significantly correlated with the detection of early UGIC. This parameter can be considered as an effective indicator for assessing the quality of EGD.

As a fundamental thermoelectric phenomenon in many solid-state materials, the Nernst effect has yet to be observed in conducting polymers. This knowledge could provide important insight into their elusive mechanism, which are crucial for flexible optoelectronic and thermoelectric applications. However, within the Landau’s Fermi-liquid picture, the Nernst coefficient has demonstrated to be proportional to the charge mobility, and thus should be negligible in less ordered polymers with inherent low mobility. Here, we challenge this notion by observing an anomalously large Nernst effect in a range of conducting polymers. Specially, the Nernst coefficients in these doped polymers exceed the Fermi-liquid predictions by 2-3 orders of magnitudes with negative mobility dependence. These intriguing observations are attributed to the intrinsic quasi-one-dimensional transport nature in conjugated polymers and their unique chemical doping mechanism. Our research not only provides experimental insights into the non-Fermi-liquid charge transport nature of polymers, but also suggests its universality for other quasi-one-dimensional materials and/or less ordered systems, and opens up exciting possibilities for developing transverse organic thermoelectric applications. The Nernst effect of transverse thermoelectric flow is usually small in less ordered systems with low charge mobility. Here, the authors show that conjugated polymers defy this expectation with Nernst effects orders of magnitude larger than predicted.

Accelerated repair of Achilles tendon rupture and prevention of re-rupture continue to pose significant technical challenges in orthopedic surgery and rehabilitation. Extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells exhibit substantial therapeutic potential for various degenerative diseases and tissue regeneration. However, the use of EVs alone for repairing ruptured Achilles tendons requires multiple invasive administrations, such as repeated injections, to maintain a therapeutic effect, which increases patient discomfort and the risk of infection. In this study, we innovatively combined EVs with sodium alginate-based piezoelectric hydrogel (SPH) to develop SPH-EVs. By leveraging the slow degradation of SPH in vivo, SPH-EVs enable sustained-release of EVs while generating electrical stimulation, ensuring that an effective therapeutic concentration is maintained at the Achilles tendon fracture site. Additionally, the integrated near-field communication (NFC) module within SPH-EVs allows for real-time monitoring of rehabilitation exercise intensity in the affected area, guiding patients to conduct rehabilitation training within a safe range and minimizing the risk of re-rupture. Graphical Abstract

BackgroundHeterotopic gastric mucosa in the upper esophagus (HGMUE) is considered to be accompanied by pharyngolaryngeal symptoms, whereas the association strength between HGMUE and pharyngolaryngeal symptoms remains controversial. This study assessed the strength of the association between HGMUE and pharyngolaryngeal symptoms using a meta-analytic approach.MethodsPubMed, Embase, Web of Science, and CNKI databases were searched for relevant articles published between January 2010 and January 2024. The pharyngolaryngeal symptoms of chronic cough, dysphagia, hoarseness, and globus in patients with HGMUE were summarized. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model. The exploratory analyses were also performed, including sensitivity and subgroup analyses.ResultsA total of 17 observational studies (1 cohort study and 16 cross-sectional studies) with 626,369 patients (2414 HGMUE patients and 623,955 non-HGMUE patients) were included in the meta-analysis. HGMUE was significantly associated with an elevated incidence of chronic cough (OR: 3.36; 95% CI 1.25–9.01; P = 0.02), dysphagia (OR: 1.58; 95% CI 1.12–2.25; P = 0.01), hoarseness (OR: 4.13; 95% CI 1.47–11.56; P = 0.007), and globus (OR: 2.41; 95% CI: 1.43–4.04, P < 0.001). The association between HGMUE and the risk of dysphagia was found to be potentially influenced by study design, sample size, country, and diagnostic method, whereas the association between HGMUE with the risk of globus was potentially affected by the study design and country.ConclusionHGMUE was significantly associated with chronic cough, dysphagia, hoarseness, and globus. HGMUE should be taken into consideration for patients with pharyngolaryngeal symptoms.

Childhood trauma has been increasingly recognised as an important environmental risk factor in the development and maintenance of obsessive-compulsive disorder (OCD). However, the specific ways in which different trauma types influence distinct OCD symptom dimensions remain unclear. This study aimed to investigate the multidimensional impact of childhood trauma on OCD using a network analysis approach. A total of 410 patients with OCD participated in this study. Factor analysis and exploratory graph analysis were conducted to identify symptom dimensions. Network analysis was used to explore connections between childhood trauma types and symptom dimensions. Four distinct symptom dimensions were identified: , , , and . exhibited the strongest connectivity in the network and served as a key bridge linking childhood trauma to psychopathology. Among the childhood trauma types, emotional abuse and physical neglect demonstrated the highest bridge centrality, highlighting their substantial impact on OCD development and persistence. Network Comparison Tests indicated no significant sex differences in network structure, global strength, or centrality. Emotional abuse and physical neglect appear to impact OCD symptomatology primarily through emotional dysfunction. These findings emphasise the need for incorporating emotion-focused strategies and trauma-informed interventions into OCD treatment protocols. Longitudinal studies are warranted to better understand the causal relationships between childhood trauma, emotional dysregulation, and OCD.