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BACKGROUND: The amoxicillin dose used in dual therapy to eradicate Helicobacter pylori varies across studies and the optimal amoxicillin dose for vonoprazan-based dual therapies remains unclear. We aimed to investigate the efficacy and safety of low- and high-dose amoxicillin in vonoprazan-amoxicillin dual therapy. MATERIALS AND METHODS: A comprehensive systematic review was conducted by searching databases from inception to October 2023. All trials that evaluated the effectiveness and safety of vonoprazan-amoxicillin dual therapy for eradicating H. pylori were included. Pooled eradication rate, incidence of adverse events, relative risks, and 95% confidence intervals are presented. RESULTS: Eighteen studies with 12 low-dose amoxicillin (VLA) and 13 high-dose amoxicillin (VHA) arms were included. The pooled eradication rates were 82.4% and 86.8% for VLA therapy, and 86.0% and 90.9% for VHA therapy by the intention-to-treat and per-protocol analyses, respectively. In the subgroup analysis stratified by duration, the eradication rates achieved in 7 days, 10 days, and 14 days treatments with VLA and VHA dual therapies were 80.8%, 84.2%, 83.1%, and 67.3%, 88.8%, 87.5%, respectively. In the four randomized controlled trials that directly compared VLA and VHA dual therapies, the efficacy was not statistically different in the intention-to-treat (76.9% vs 81.4%, p = 0.337) and per-protocol (81.6% vs 84.0%, p = 0.166) analyses. Additionally, the incidence of adverse events (p = 0.965) and compliance (p = 0.994) were similar in both groups. CONCLUSION: VLA therapy demonstrated comparable efficacy and safety to VHA therapy, along with regional differences. An appropriately extended treatment duration may be critical for therapeutic optimization of vonoprazan-amoxicillin treatment.
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Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Pirroles , Sulfonamidas , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Pirroles/administración & dosificación , Pirroles/uso terapéutico , Pirroles/efectos adversos , Helicobacter pylori/efectos de los fármacos , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Resultado del Tratamiento , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/efectos adversosRESUMEN
BACKGROUND: Large language models (LLMs) are promising medical counseling tools, but the reliability of responses remains unclear. We aimed to assess the feasibility of three popular LLMs as counseling tools for Helicobacter pylori infection in different counseling languages. MATERIALS AND METHODS: This study was conducted between November 20 and December 1, 2023. Three large language models (ChatGPT 4.0 [LLM1], ChatGPT 3.5 [LLM2], and ERNIE Bot 4.0 [LLM3]) were input 15 H. pylori related questions each, once in English and once in Chinese. Each chat was conducted using the "New Chat" function to avoid bias from correlation interference. Responses were recorded and blindly assigned to three reviewers for scoring on three established Likert scales: accuracy (ranged 1-6 point), completeness (ranged 1-3 point), and comprehensibility (ranged 1-3 point). The acceptable thresholds for the scales were set at a minimum of 4, 2, and 2, respectively. Final various source and interlanguage comparisons were made. RESULTS: The overall mean (SD) accuracy score was 4.80 (1.02), while 1.82 (0.78) for completeness score and 2.90 (0.36) for comprehensibility score. The acceptable proportions for the accuracy, completeness, and comprehensibility of the responses were 90%, 45.6%, and 100%, respectively. The acceptable proportion of overall completeness score for English responses was better than for Chinese responses (p = 0.034). For accuracy, the English responses of LLM3 were better than the Chinese responses (p = 0.0055). As for completeness, the English responses of LLM1 was better than the Chinese responses (p = 0.0257). For comprehensibility, the English responses of LLM1 was better than the Chinese responses (p = 0.0496). No differences were found between the various LLMs. CONCLUSIONS: The LLMs responded satisfactorily to questions related to H. pylori infection. But further improving completeness and reliability, along with considering language nuances, is crucial for optimizing overall performance.
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Consejo , Infecciones por Helicobacter , Helicobacter pylori , Lenguaje , Humanos , Infecciones por Helicobacter/diagnóstico , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection. METHODS: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. CONCLUSION: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05431075.
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Antibacterianos , Bismuto , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Tetraciclina , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Tetraciclina/uso terapéutico , Tetraciclina/administración & dosificación , Tetraciclina/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Bismuto/uso terapéutico , Bismuto/efectos adversos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Adulto , Helicobacter pylori/efectos de los fármacos , Resultado del Tratamiento , China , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Esquema de Medicación , Esomeprazol/uso terapéutico , Esomeprazol/administración & dosificación , Anciano , Adulto Joven , Pruebas Respiratorias , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversosRESUMEN
BACKGROUND AND AIM: The study aims to evaluate the feasibility of body mass index (BMI)-based individualized small bowel preparation for computed tomography enterography (CTE). METHODS: In this prospective randomized controlled study, patients undergoing CTE were randomly assigned to the individualized group or standardized group. Those in individualized group were given different volumes of mannitol solution based on BMI (1000 mL for patients with BMI < 18.5 kg/m2, 1500 mL for patients with 18.5 kg/m2 ≤ BMI < 25 kg/m2 and 2000 mL for patients with BMI ≥ 25 kg/m2) while patients in the standardized group were all asked to consume 1500-mL mannitol solution. CTE images were reviewed by two experienced radiologists blindly. Each segment of the small bowel was assessed for small bowel image quality and disease detection rates. Patients were invited to record a diary regarding adverse events and acceptance. RESULTS: A total of 203 patients were enrolled and randomly divided into two groups. For patients with BMI < 18.5 kg/m2, 1000-mL mannitol solution permitted a significantly lower rate of flatulence (P = 0.045) and defecating frequency (P = 0.011) as well as higher acceptance score (P = 0.015), but did not affect bowel image quality and diseases detection compared with conventional dosage. For patients with BMI ≥ 25 kg/m2, 2000-mL mannitol solution provided better overall image quality (P = 0.033) but comparable rates of adverse events and patients' acceptance compared with conventional dosage. CONCLUSIONS: Individualized bowel preparation could achieve both satisfactory image quality and patients' acceptance thus might be an acceptable alternative in CTE.
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Índice de Masa Corporal , Intestino Delgado , Manitol , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Manitol/administración & dosificación , Manitol/efectos adversos , Tomografía Computarizada por Rayos X/métodos , Intestino Delgado/diagnóstico por imagen , Adulto , Anciano , Estudios de Factibilidad , Catárticos/administración & dosificación , Catárticos/efectos adversos , Medicina de PrecisiónRESUMEN
BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).
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Amoxicilina , Antibacterianos , Bismuto , Claritromicina , Esquema de Medicación , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Sulfonamidas , Tetraciclina , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/efectos de los fármacos , Persona de Mediana Edad , Masculino , Femenino , Tetraciclina/administración & dosificación , Tetraciclina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Bismuto/administración & dosificación , Bismuto/uso terapéutico , Bismuto/efectos adversos , Adulto , Claritromicina/administración & dosificación , Amoxicilina/administración & dosificación , Sulfonamidas/administración & dosificación , Pirroles/administración & dosificación , Pirroles/efectos adversos , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Pruebas Respiratorias , Resultado del Tratamiento , Anciano , ChinaRESUMEN
This study represents the first analysis of the bacterial community in chickens affected by swollen head syndrome, utilizing 16S rRNA gene sequencing. Samples were obtained from clinical laying chickens and were examined for the presence of Avibacterium paragallinarum (APG) and Ornithobacterium rhinotracheale (ORT) using conventional polymerase chain reaction (PCR). From the samples, five APG-positive (APG) and APG-negative (N-APG) samples were chosen, along with five specific pathogen-free chickens, for 16S rRNA gene sequencing. Results showed that APG and ORT were widely detected in the chicken samples with swollen head syndrome (SHS, 9/10), while APG was detected in all five specific pathogen-free (SPF) samples. In contrast, conventional PCR sensitivity was found to be inadequate for diagnosis, with only 35.7% (5/14) and 11.1% (1/9) sensitivity for APG and ORT, respectively, based on 16S rRNA gene sequencing data. Furthermore, 16S rRNA gene sequencing was able to quantify the bacteria in the samples, revealing that the relative abundance of APG in the APG group ranged from 2.7 to 81.3%, while the relative abundance of APG in the N-APG group ranged from 0.1 to 21.0%. Notably, a low level of APG was also detected in all 5 SPF samples. The study also identified a significant number of animal and human common bacterial pathogens, including but not limited to Gallibacterium anatis, Riemerella columbina, Enterococcus cecorum, Mycoplasma synoviae, Helicobacter hepaticus, and Staphylococcus lentus. In conclusion, 16S rRNA gene sequencing is a valuable tool for bacterial pathogen diagnosis and the discovery of novel bacterial pathogens, while conventional PCR is not reliable for diagnosis.
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Pollos , Reacción en Cadena de la Polimerasa , Enfermedades de las Aves de Corral , ARN Ribosómico 16S , ARN Ribosómico 16S/genética , Animales , Pollos/microbiología , Reacción en Cadena de la Polimerasa/métodos , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/diagnóstico , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , ADN Bacteriano/genética , Análisis de Secuencia de ADN , FilogeniaRESUMEN
Wound healing is a complex and error-prone process. Wound healing in adults often leads to the formation of scars, a type of fibrotic tissue that lacks skin appendages. Hypertrophic scars and keloids can also form when the wound-healing process goes wrong. Leptin (Lep) and leptin receptors (LepRs) have recently been shown to affect multiple stages of wound healing. This effect, however, is paradoxical for scarless wound healing. On the one hand, Lep exerts pro-inflammatory and profibrotic effects; on the other hand, Lep can regulate hair follicle growth. This paper summarises the role of Lep and LepRs on cells in different stages of wound healing, briefly introduces the process of wound healing and Lep and LepRs, and examines the possibility of promoting scarless wound healing through spatiotemporal, systemic, and local regulation of Lep levels and the binding of Lep and LepRs.
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Cicatriz Hipertrófica , Leptina , Humanos , Cicatriz Hipertrófica/patología , Leptina/metabolismo , Receptores de Leptina/metabolismo , Piel/metabolismo , Cicatrización de Heridas , AnimalesRESUMEN
BACKGROUND AND AIM: After three treatment failures, Helicobacter pylori infection is deemed refractory as antibiotic treatment options become significantly limited. This study evaluated the efficacy and safety of a 14-day modified concomitant therapy for managing refractory H. pylori infection. METHODS: Patients who had failed to respond to three or more rounds of H. pylori therapies were recruited for this study. They received a 14-day modified concomitant therapy, including esomeprazole 40 mg, amoxicillin 1000 mg, and furazolidone 100 mg twice daily and tetracycline 500 mg four times daily. Demographic data, adverse events, and patient compliance were recorded. The presence of H. pylori was reevaluated 6 weeks following treatment. Eradication rate was assessed as the primary outcome. RESULTS: Overall, 59 participants received the 14-day modified concomitant therapy. In the intention-to-treat and per-protocol analyses, the eradication rate was 84.7% (50/59) and 89.3% (50/56), respectively. H. pylori was successfully isolated from 75.0% (12/16) of patients. The resistance rate of H. pylori to metronidazole, levofloxacin, and clarithromycin was 91.7% (11/12), 58.3% (7/12), and 50.0% (6/12), respectively. Resistance to amoxicillin, furazolidone, or tetracycline was not observed. The frequency of adverse events was 35.6% (21/59), with no serious adverse events reported. CONCLUSION: The 14-day modified concomitant therapy appears to be appropriate for refractory H. pylori infection and is particularly promising for the Chinese population. A randomized controlled trial is warranted to verify its efficacy, especially in the current environment of increasing antibiotic resistance.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/etiología , Proyectos Piloto , Furazolidona/efectos adversos , Quimioterapia Combinada , Antibacterianos , Amoxicilina , Metronidazol , Claritromicina/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Lugol chromoendoscopy is the standard technique to detect an esophageal squamous cell carcinoma (ESCC). However, a high concentration of Lugol's solution can induce mucosal injury and adverse events. We aimed to investigate the optimal concentration of Lugol's solution to reduce mucosal injury and adverse events without degrading image quality. METHODS: This was a two-phase double-blind randomized controlled trial. In phase I, 200 eligible patients underwent esophagogastroduodenoscopy and then were randomly (1:1:1:1:1) sprayed with 1.2%, 1.0%, 0.8%, 0.6%, or 0.4% Lugol's solution. Image quality, gastric mucosal injury, adverse events, and operation satisfaction were compared to investigate the minimal effective concentration. In phase II, 42 cases of endoscopic mucosectomy for early ESCC were included. The patients were randomly assigned (1:1) to the minimal effective (0.6%) or conventional (1.2%) concentration of Lugol's solution for further comparison of the effectiveness. RESULTS: In phase I, the gastric mucosal injury was significantly reduced in 0.6% group (P < 0.05). Furthermore, there was no statistical significance in image quality between 0.6% and higher concentrations of Lugol's solution (P > 0.05, respectively). It also showed that the operation satisfaction decreased in 1.2% group compared with the lower concentration groups (P < 0.05). In phase II, the complete resection rate was 100% in both groups, while 0.6% Lugol's solution showed higher operation satisfaction (W = 554.500, P = 0.005). CONCLUSIONS: The study indicates that 0.6% might be the optimal concentration of Lugol's solution for early detection and delineation of ESCC, considering minimal mucosal injury and satisfied image. The registry of clinical trials: ClinicalTrials.gov (NCT03180944).
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Neoplasias Esofágicas/patología , Esofagoscopía/métodos , ColorantesRESUMEN
INTRODUCTION: Vonoprazan, a novel potassium-competitive acid blocker, has a strong acid suppression effect and potent efficacy in acid-associated diseases, including Helicobacter pylori eradication. We performed a systematic review and meta-analysis to investigate the efficacy and safety of vonoprazan/amoxicillin dual therapy for H. pylori eradication. METHODS: We conducted a systematic literature search through PubMed, Web of Science, EMBASE, and the Cochrane Library up to June 2022, to identify randomized controlled trials and cohort studies comparing vonoprazan/amoxicillin dual therapy and triple therapies for H. pylori eradication. Primary outcomes were cure rates and relative efficacy. Secondary outcomes included adverse events, dropout rate, and subgroup analysis. RESULTS: Five studies with 1,852 patients were included in the analysis. The cure rates of vonoprazan/amoxicillin dual therapy were 85.6% with 95% confidence interval (CI) of 79.7-91.5% and 88.5% (95% CI: 83.2-93.8%) in the intention-to-treat and per-protocol analyses. The efficacy of vonoprazan/amoxicillin dual therapy was not inferior to that of triple therapy with pooled risk ratio (RR) of 1.03 (95% CI: 0.97-1.10) and 1.02 (95% CI: 0.98-1.08) in intention-to-treat and per-protocol analyses; while it was significantly superior to the omeprazole or lansoprazole-based triple therapy (RR = 1.15, 95% CI: 1.05-1.25, p = 0.001). For clarithromycin-resistant strains, vonoprazan/amoxicillin dual therapy showed superiority to vonoprazan-based triple therapy (86.7% vs. 71.4%, RR = 1.20, 95% CI: 1.03-1.39, p = 0.02); however, vonoprazan/amoxicillin dual therapy was significant inferior to vonoprazan-based triple therapy for clarithromycin-sensitive strains (83.0% vs. 92.8%, RR = 0.90, 95% CI: 0.85-0.95, p = 0.0002). The adverse effects of vonoprazan/amoxicillin dual therapy were lower than those of triple therapy (21.2% vs. 26.5%, RR = 0.86, 95% CI: 0.73-1.01, p = 0.06), especially the incidence of diarrhea (p = 0.01). CONCLUSIONS: The efficacy of vonoprazan/amoxicillin dual therapy is noninferior to vonoprazan-based triple therapy but superior to the omeprazole or lansoprazole-based triple therapy and has less side effects. Patients with clarithromycin-resistant strains are particularly expected to benefit from vonoprazan/amoxicillin dual therapy.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Amoxicilina/uso terapéutico , Claritromicina/uso terapéutico , Antibacterianos/efectos adversos , Infecciones por Helicobacter/tratamiento farmacológico , Inhibidores de la Bomba de Protones/efectos adversos , Quimioterapia Combinada , Pirroles/efectos adversos , Lansoprazol/farmacología , Lansoprazol/uso terapéutico , Omeprazol/farmacología , Omeprazol/uso terapéutico , Resultado del TratamientoRESUMEN
The loss of dermal white adipose tissue (dWAT) is vital to the formation of dermal fibrosis (DF), but the specific mechanism is not well understood. A few studies are reviewed to explore the role of dWAT in the formation of DF. Recent findings indicated that the adipocytes-to-myofibroblasts transition in dWAT reflects the direct contribution to the DF formation. While adipose-derived stem cells (ADSCs) contained in dWAT express antifibrotic cytokines, the loss of ADSCs leads to skin protection decreased, which indirectly exacerbates DF and tissue damage. Therefore, blocking or reversing the adipocytes-to-myofibroblasts transition or improving the survival of ADSCs in dWAT and the expression of antifibrotic cytokines may be an effective strategy for the treatment of DF.
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Adipocitos , Tejido Adiposo Blanco , Adipocitos/metabolismo , Tejido Adiposo , Tejido Adiposo Blanco/metabolismo , Citocinas/metabolismo , Fibrosis , Humanos , Miofibroblastos/metabolismoRESUMEN
BACKGROUND: Helicobacter pylori (H. pylori) infections are of serious concern due to the associated risk of gastric cancer. However, many patients have poor medication and therapy compliance, which makes it difficult to eradicate their infections. This points to the need for stronger educational interventions aimed at enhancing compliance, thus increasing the potential for treatment success. As such, this study conducted a meta-analysis to clarify the effects of enhanced patient education (EPE) programs for H. pylori. MATERIALS AND METHODS: We searched electronic databases (PubMed, EMBASE, Web of Science, and Cochrane Library) for randomized controlled trials (RCTs) on health education for patients infected with H. pylori from inception to June 2021. The primary outcome was the eradication rate of H. pylori, while the secondary outcomes included the incidence of individual adverse symptoms, treatment compliance, clinical symptom remission after treatment, and patient satisfaction. We used the fixed or random-effects model to pool the risk ratio (RR), with 95% confidence interval. We also conducted sensitivity and subgroup analyses. RESULTS: Our search returned seven relevant studies across a total of 1,433 patients. Compared with controls, EPE was significantly associated with improved H. pylori eradication rates (RR = 1.16, 95%CI: 1.04-1.29, p = 0.006) and patient compliance (RR = 1.48, 95%CI: 1.14-1.93, p = 0.003). A subgroup analysis also showed that EPE benefits were consistent across patients with different eradication programs, WeChat intervention plans, and intervention frequencies (p < 0.05). However, there were no significant differences in the total adverse effects, common side effects (diarrhea, nausea, abdominal pain, taste disorder, and skin rash), or discontinuation rate (p > 0.05). CONCLUSIONS: Patient education is inexpensive, safe, and convenient. In this context, our findings suggest that enhanced educational interventions have positive effects on both the H. pylori eradication rate and adherence among infected patients, and thus constitute promising complements to clinical treatment regimens.
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Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Antibacterianos/farmacología , Quimioterapia Combinada , Infecciones por Helicobacter/diagnóstico , Humanos , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
A phytochemical investigation on the roots of medicinal plant Eurycoma longifolia resulted in the isolation of 10 new highly oxygenated C20 quassinoids longifolactones GâP (1-10), along with four known ones (11-14). Their chemical structures and absolute configurations were unambiguously elucidated on the basis of comprehensive spectroscopic analysis and X-ray crystallographic data. Notably, compound 1 is a rare pentacyclic C20 quassinoid featuring a densely functionalized 2,5-dioxatricyclo[5.2.2.04,8]undecane core. Compound 4 represents the first example of quassinoids containing a 14,15-epoxy functionality, and 7 features an unusual α-oriented hydroxyl group at C-14. All isolated compounds were evaluated for their anti-proliferation activities on human leukemia cells. Among the isolates, compounds 5, 12, 13, and 14 potently inhibited the in vitro proliferation of K562 and HL-60 cells with IC50 values ranging from 2.90 to 8.20 µM.
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Antineoplásicos Fitogénicos/farmacología , Eurycoma/química , Leucemia/tratamiento farmacológico , Extractos Vegetales/farmacología , Raíces de Plantas/química , Cuassinas/farmacología , Proliferación Celular , Células HL-60 , Humanos , Células K562 , Leucemia/patologíaRESUMEN
Phosphoinositide-3 kinase signaling modulates many cellular processes, including cell survival, proliferation, differentiation, and apoptosis. Currently, it is known that the establishment of respiratory syncytial virus infection requires phosphoinositide-3 kinase signaling. However, the regulatory pattern of phosphoinositide-3 kinase signaling or its corresponding molecular mechanism during respiratory syncytial virus entry remains unclear. Here, the involvement of phosphoinositide-3 kinase signaling in respiratory syncytial virus entry was studied. PIK-24, a novel compound designed with phosphoinositide-3 kinase as a target, had potent anti-respiratory syncytial virus activity both in vitro and in vivo PIK-24 significantly reduced viral entry into the host cell through blocking the late stage of the fusion process. In a mouse model, PIK-24 effectively reduced the viral load and alleviated inflammation in lung tissue. Subsequent studies on the antiviral mechanism of PIK-24 revealed that viral entry was accompanied by phosphoinositide-3 kinase signaling activation, downstream RhoA and cofilin upregulation, and actin cytoskeleton rearrangement. PIK-24 treatment significantly reversed all these effects. The disruption of actin cytoskeleton dynamics or the modulation of phosphoinositide-3 kinase activity by knockdown also affected viral entry efficacy. Altogether, it is reasonable to conclude that the antiviral activity of PIK-24 depends on the phosphoinositide-3 kinase signaling and that the use of phosphoinositide-3 kinase signaling to regulate actin cytoskeleton rearrangement plays a key role in respiratory syncytial virus entry.
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Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Animales , Ratones , Fosfatidilinositoles , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Transducción de Señal , Internalización del VirusRESUMEN
BACKGROUND AND AIM: Cresyl violet (CV) is a topical dye that allows simultaneous chromoendoscopy and in vivo confocal laser endomicroscopy in identification of neoplastic changes of the lower gastrointestinal tract without intravenous injection of fluorescein, but as yet no investigation has reported its application in the diagnosis of gastric intestinal metaplasia (GIM). This study aims to assess the feasibility as well as diagnosis accuracy of topical CV for in vivo diagnosis of GIM by using probe-based confocal laser endomicroscopy (pCLE). METHODS: In this prospective, open-label, feasibility study, 129 confocal videos from 22 patients with known GIM were analyzed and compared with corresponding histological images to establish the CV staining characteristics. In addition, 47 patients with known or suspected GIM were prospectively enrolled to evaluate the accuracy of this topical CV endomicroscopic imaging. RESULTS: Probe-based confocal laser endomicroscopy with topical CV enabled clear visualization of the goblet cells, absorptive cells, and intestinal villi of GIM. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of pCLE diagnosis of GIM on a per-location analysis was 93.01%, 91.95%, 93.51%, 86.96%, and 96.11%, respectively. The intraclass correlation coefficient for inter-observer agreement and mean kappa value for intra-observer agreement for the diagnosis of GIM was 0.82 and 0.87, respectively. CONCLUSIONS: Topical CV enables real-time chromoendoscopy in conjunction with pCLE examination of the stomach and warrants accurate diagnosis of GIM. It may be an acceptable and potentially alternative dye for confocal imaging in the future.
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Benzoxazinas , Medios de Contraste , Enfermedades Gastrointestinales/diagnóstico por imagen , Metaplasia/diagnóstico por imagen , Microscopía Confocal/métodos , Adulto , Anciano , Femenino , Enfermedades Gastrointestinales/patología , Humanos , Masculino , Metaplasia/patología , Persona de Mediana EdadAsunto(s)
Vesículas Extracelulares , Cicatrización de Heridas , Ratas , Animales , Piel/irrigación sanguíneaAsunto(s)
Abdominoplastia , Hipertensión , Mamoplastia , Humanos , Losartán , Cicatriz/tratamiento farmacológico , Cicatriz/etiología , Cicatriz/prevención & control , Cicatrización de Heridas , Abdominoplastia/efectos adversos , Mamoplastia/efectos adversos , Método Doble Ciego , Resultado del TratamientoRESUMEN
Severe acute respiratory syndrome coronavirus-2 is a highly contagious positive-sense, single-stranded RNA virus that has rapidly spread worldwide. As of December 17, 2023, 772838745 confirmed cases including 6988679 deaths have been reported globally. This virus primarily spreads through droplets, airborne transmission, and direct contact. Hospitals harbor a substantial number of confirmed coronavirus disease 2019 (COVID-19) patients and asymptomatic carriers, accompanied by high population density and a larger susceptible population. These factors serve as potential triggers for nosocomial infections, posing a threat during the COVID-19 pandemic. Nosocomial infections occur to varying degrees across different countries worldwide, emphasizing the urgent need for a practical approach to prevent and control the intra-hospital spread of COVID-19. This study primarily concentrated on a novel strategy combining preventive measures with treatment for combating COVID-19 nosocomial infections. It suggests preventive methods, such as vaccination, disinfection, and training of heathcare personnel to curb viral infections. Additionally, it explored therapeutic strategies targeting cellular inflammatory factors and certain new medications for COVID-19 patients. These methods hold promise in rapidly and effectively preventing and controlling nosocomial infections during the COVID-19 pandemic and provide a reliable reference for adopting preventive measures in the future pandemic.
RESUMEN
Background: Our study aimed to develop a nomogram incorporating cytokeratin fragment antigen 21-1 (CYFRA21-1) to assist in differentiating between patients with intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). Methods: A total of 487 patients who were diagnosed with ICC and HCC at Qilu Hospital of Shandong University were included in this study. The patients were divided into a training cohort and a validation cohort based on whether the data collection was retrospective or prospective. Univariate and multivariate analyses were employed to select variables for the nomogram. The discrimination and calibration of the nomogram were evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Decision curve analysis (DCA) was used to assess the nomogram's net benefits at various threshold probabilities. Results: Six variables, including CYFRA21-1, were incorporated to establish the nomogram. Its satisfactory discriminative ability was indicated by the AUC (0.972 for the training cohort, 0.994 for the validation cohort), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) values. The Hosmer-Lemeshow test and the calibration plots demonstrated favorable consistency between the nomogram predictions and the actual observations. Moreover, DCA revealed the clinical utility and superior discriminative ability of the nomogram compared to the model without CYFRA21-1 and the model consisting of the logarithm of alpha-fetoprotein (Log AFP) and the logarithm of carbohydrate antigen 19-9 (Log CA19-9). Additionally, the AUC values suggested that the discriminative ability of Log CYFRA21-1 was greater than that of the other variables used as diagnostic biomarkers. Conclusions: This study developed and validated a nomogram including CYFRA21-1, which can aid clinicians in the differential diagnosis of ICC and HCC patients.