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1.
Am J Gastroenterol ; 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39382581

RESUMEN

BACKGROUND: Visual endoscopic retrograde appendicitis therapy (V-ERAT) involves a Single-use Video Scope, allowing real-time visualization of the appendiceal lumen during the procedure to treat uncomplicated acute appendicitis (AA). This study aims to compare V-ERAT to antibiotic therapy in treating uncomplicated AA. METHODS: This multicenter, retrospective cohort study was conducted at nine hospitals in China from August 2021 to July 2023. Propensity score matching was performed to minimize selection bias. A total of 692 uncomplicated AA patients were included, with 188 undergoing V-ERAT and 504 receiving antibiotic therapy. The primary outcome was treatment success rate. The secondary outcomes included recurrent appendicitis rate, the appendectomy rate during the initial hospitalization, length of initial hospitalization, time to disease recurrence, and overall adverse events. RESULTS: The treatment success rate did not differ between the V-ERAT and antibiotic groups (93.6%; 95% confidence interval [CI] 89.1% to 96.7% vs. 90.5%; 95% CI, 87.6% to 92.9%) ( P = 0.225). However, V-ERAT demonstrated a significantly lower risk of appendicitis recurrence compared to antibiotic therapy during the follow-up (log-rank P < 0.001), with a hazard ratio of 0.14 (95% CI 0.07-0.29, P < 0.001). V-ERAT was associated with a lower appendectomy rate during the initial hospitalization (4.3%; 95% CI, 1.9% to 8.2% vs. 9.5%; 95% CI, 7.1 to 12.4%) (P = 0.027), a shorter length of initial hospitalization (3 [IQR, 3-4] vs. 4 [IQR, 4-6] days, P < 0.001), and a longer time to recurrence (269 [IQR, 210-318] vs. 70 [IQR, 21-103] days, P < 0.001). The overall adverse event rates did not differ between the two groups (log-rank P = 0.064). CONCLUSION: V-ERAT appears to be a safe and effective alternative to antibiotic therapy in treating uncomplicated AA, significantly reducing the risk of appendicitis recurrence.

2.
J Biomater Appl ; : 8853282241279340, 2024 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-39440835

RESUMEN

Brucellosis is an intracellular infectious disease that is primarily treated with antibacterial therapy. However, most antibacterial drugs struggle to penetrate the cell membrane and may be excluded or inactivated within the cell. In a recent study, researchers developed a nanogel coated with polydopamine (PDA) that responds to reactive oxygen species (ROS) and has enhanced adhesion properties. This nanogel encapsulates photosensitized zinc phthalocyanine (ZnPc) and an antibacterial drug, and is further modified with folic acid (FA) for active targeting. The resulting ROS-responsive nanogel, termed PDA@PMAA@ZnPc@DH-FA, can reach temperatures up to 50°C under near-infrared light, leading to a 72.1% improvement in drug release through increased ROS production. Cell staining confirmed a cell survival rate above 75%, with a low hemolysis rate of only 4.633%, indicating excellent biocompatibility. Furthermore, the study's results showed that the nanogel exhibited stronger killing effects against Brucella compared to administering the drug alone. Under near-infrared irradiation, the nanogel achieved a bacteriostatic rate of 99.8%. The combined approach of photothermal therapy and photodynamic therapy offers valuable insights for treating Brucella.

3.
J Immunother Cancer ; 12(10)2024 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-39455095

RESUMEN

BACKGROUND: Cervical cancer remains a global health challenge. The identification of new immunotherapeutic targets may provide a promising platform for advancing cervical cancer treatment. OBJECTIVE: This study aims to investigate the role of CUB domain-containing protein 1 (CDCP1) in cervical cancer progression and evaluate its potential as a therapeutic target. METHODS: We performed comprehensive analyses using patient cohorts and preclinical models to examine the association between CDCP1 expression and cervical cancer prognosis. Then in immunodeficient and immunocompetent mouse models, we further investigated the impact of CDCP1 on the tumor immune microenvironment, focusing on its effects on tumor-infiltrating T cells, including cytotoxic T lymphocytes (CTLs) and regulatory T cells (Tregs). Mechanistic studies were performed to elucidate the pathways involved in CDCP1-mediated immune modulation, in particular its interaction with the T cell receptor CD6 and the activation of the JAK-STAT signaling pathway. RESULTS: Our results show that CDCP1 overexpression is associated with poor prognosis and T cell infliction in cervical cancer. Specifically, it affects the activity of CTLs and Tregs. Mechanistically, CDCP1 binds to CD6 and inhibits the JAK-STAT pathway of T cells. The study further demonstrates that targeting CDCP1 with the inhibitor 8-prenylnaringenin (8PN) effectively suppresses tumor growth in vivo and enhances antitumor immunity. CONCLUSIONS: CDCP1 plays a critical role in cervical cancer progression by modulating the tumor immune microenvironment. Targeting CDCP1 offers a promising therapeutic strategy to improve the outcome of patients with cervical cancer.


Asunto(s)
Transducción de Señal , Neoplasias del Cuello Uterino , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Femenino , Humanos , Animales , Ratones , Quinasas Janus/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Factores de Transcripción STAT/metabolismo , Microambiente Tumoral , Antígenos CD/metabolismo , Moléculas de Adhesión Celular/metabolismo , Línea Celular Tumoral , Antígenos de Neoplasias
4.
Sensors (Basel) ; 24(20)2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39460096

RESUMEN

Antioxidants are substances that have the ability to resist or delay oxidative damage. Antioxidants can be used not only for the diagnosis and prevention of vascular diseases, but also for food preservation and industrial production. However, due to the excessive use of antioxidants, it can cause environmental pollution and endanger human health. It can be seen that the development of antioxidant detection technology is important for environment/health maintenance. It is found that traditional detection methods, including high performance liquid chromatography, gas chromatography, etc., have shortcomings such as cumbersome operation and high cost. In contrast, the nanozyme-based detection method features advantages of low cost, simple operation, and rapidity, which has been widely used in the detection of various substances such as glucose and antioxidants. This article focuses on the latest research progress of nanozymes for antioxidant detection. Nanozymes for antioxidant detection are classified according to enzyme-like types. Different types of nanozyme-based sensing strategies and detection devices are summarized. Based on the summary and analysis, one can find that the development of commercial nanozyme-based devices for the practical detection of antioxidants is still challenging. Some emerging technologies (such as artificial intelligence) should be fully utilized to improve the detection sensitivity and accuracy. This article aims to emphasize the application prospects of nanozymes in antioxidant detection and to provide new ideas and inspiration for the development of detection methods.


Asunto(s)
Antioxidantes , Técnicas Biosensibles , Antioxidantes/análisis , Técnicas Biosensibles/métodos , Humanos , Nanoestructuras/química , Enzimas/química
5.
Surv Ophthalmol ; 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39368555

RESUMEN

Suprachoroidal hemorrhage (SCH) is a potentially visually devastating complication of intraocular surgery, but estimates of perioperative SCH incidence vary. We performed a systematic review and meta-analysis of perioperative SCH incidence among population-based studies published between 1990 and 2023. Thirty-five studies collectively reported 1657 cases of perioperative SCH from a population of 3,028,911 surgeries. The estimated incidence of SCH was 0.12 % (95 % CI, 0.10-0.14 %), or about 1 in every 800 surgeries. The estimated incidence of perioperative massive SCH was 0.06 % (95 % CI, 0.04-0.08 %). In multivariable meta-regression, greater SCH incidence was significantly associated with smaller study population size, comparative study design, multicenter study setting, and intraoperative or delayed SCH timing (vs intraoperative alone), while lower SCH incidence was significantly associated with vitreoretinal or mixed surgery type (vs. cataract) (all P < 0.05). Study year was not a significant predictor of SCH incidence, suggesting that the incidence of SCH has not decreased over the past 3 decades despite improvements in surgical technologies and techniques. Given the rarity of SCH, and the strong effect of study population size on reported SCH incidence rates, future studies of SCH incidence should include a minimum population size of at least 1000 surgeries to obtain an accurate estimate of SCH incidence.

6.
bioRxiv ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39386646

RESUMEN

Recent advances in spatial transcriptomics technologies have led to a growing number of diverse datasets, offering unprecedented opportunities to explore tissue organizations and functions within spatial contexts. However, it remains a significant challenge to effectively integrate and interpret these data, often originating from different samples, technologies, and developmental stages. In this paper, we present INSPIRE, a deep learning method for integrative analyses of multiple spatial transcriptomics datasets to address this challenge. With designs of graph neural networks and an adversarial learning mechanism, INSPIRE enables spatially informed and adaptable integration of data from varying sources. By incorporating non-negative matrix factorization, INSPIRE uncovers interpretable spatial factors with corresponding gene programs, revealing tissue architectures, cell type distributions and biological processes. We demonstrate the capabilities of INSPIRE by applying it to human cortex slices from different samples, mouse brain slices with complementary views, mouse hippocampus and embryo slices generated through different technologies, and spatiotemporal organogenesis atlases containing half a million spatial spots. INSPIRE shows superior performance in identifying detailed biological signals, effectively borrowing information across distinct profiling technologies, and elucidating dynamical changes during embryonic development. Furthermore, we utilize INSPIRE to build 3D models of tissues and whole organisms from multiple slices, demonstrating its power and versatility.

7.
Brief Bioinform ; 25(6)2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39356327

RESUMEN

Single-cell cross-modal joint clustering has been extensively utilized to investigate the tumor microenvironment. Although numerous approaches have been suggested, accurate clustering remains the main challenge. First, the gene expression matrix frequently contains numerous missing values due to measurement limitations. The majority of existing clustering methods treat it as a typical multi-modal dataset without further processing. Few methods conduct recovery before clustering and do not sufficiently engage with the underlying research, leading to suboptimal outcomes. Additionally, the existing cross-modal information fusion strategy does not ensure consistency of representations across different modes, potentially leading to the integration of conflicting information, which could degrade performance. To address these challenges, we propose the 'Recover then Aggregate' strategy and introduce the Unified Cross-Modal Deep Clustering model. Specifically, we have developed a data augmentation technique based on neighborhood similarity, iteratively imposing rank constraints on the Laplacian matrix, thus updating the similarity matrix and recovering dropout events. Concurrently, we integrate cross-modal features and employ contrastive learning to align modality-specific representations with consistent ones, enhancing the effective integration of diverse modal information. Comprehensive experiments on five real-world multi-modal datasets have demonstrated this method's superior effectiveness in single-cell clustering tasks.


Asunto(s)
Análisis de la Célula Individual , Análisis por Conglomerados , Análisis de la Célula Individual/métodos , Humanos , Algoritmos , Microambiente Tumoral , Biología Computacional/métodos
8.
Adv Mater ; : e2407244, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39363637

RESUMEN

Soft X-ray imaging is a powerful tool to explore the structure of cells, probe material with nanometer resolution, and investigate the energetic phenomena in the universe. Conventional soft X-ray image sensors are by and large Si-based charge coupled devices that suffer from low frame rates, complex fabrication processes, mechanical inflexibility, and required cooling below -60 °C. Here, a soft X-ray photodiode is reported based on low-cost metal halide perovskite with comparable performance to commercial Si-based device. Nanothrough network electrode minimized the optical loss due to the shadowing of insensitive layers, while a multidimensional perovskite heterojunction is generated to reduce the photo-generated carrier loss. This strategy promoted a record quantum efficiency of 8 × 103% without cooling, several orders of magnitude greater than the previously achieved. Flexible and curved soft X-ray imaging arrays are fabricated based on this high-performance device structure, demonstrating stable soft X-ray response and sharp imaging capabilities. This work highlights the low-cost and efficient perovskite photodiode as a strong candidate for the next-generation soft X-ray image sensors.

9.
Ophthalmol Retina ; 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39424060

RESUMEN

OBJECTIVE: To utilize a modified intravitreal (IVT) methotrexate (MTX) protocol for the prevention of proliferative vitreoretinopathy (PVR) after silicone oil (SO) removal (SOR). DESIGN: Single-center nonrandomized retrospective comparative case series. SUBJECTS: Eyes with grade C PVR who underwent retinal detachment repair and SO placement between 2019-2022 with at least 6 months of follow-up after SOR. A control group of age- and sex-matched eyes was included. METHODS: Eyes were treated with one of two MTX protocols. Eyes in Group 1 received 6 IVT MTX injections following SO placement, and another 6 IVT MTX injections following SOR. Eyes in Group 2 received 6 IVT MTX following SO placement only. Each series of 6 IVT MTX injections (400 µg/0.1 mL) consisted of 3 injections every 2 weeks followed by 3 injections every 4 weeks. MAIN OUTCOME MEASURES: The primary outcome was the retinal attachment rate at 6 months post-SOR without re-detachment or re-operation. Secondary outcomes included change in visual acuity (VA) and rates of complications after SOR. RESULTS: Fifty-two eyes of 52 patients (13 Group 1, 13 Group 2, 26 control) (mean age 59.8 years, 80.8% male) were included with a mean follow-up of 31.0 months. In aggregate, Group 1 and Group 2 eyes received a median (IQR) of 6 (5.25, 7) IVT MTX injections pre-SOR; eyes in Group 1 received a median (IQR) of 5 (3, 6) IVT MTX injections post-SOR. Twelve (92.3%) Group 1 eyes, 11 (84.6%) Group 2 eyes, and 21 (80.8%) control eyes had primary retinal attachment at 6 months post-SOR (P > 0.05). VA outcomes did not significantly differ between groups (P > 0.05). Rates of epiretinal membrane (ERM) and cystoid macular edema (CME) were significantly lower in Group 1 eyes (7.7% and 15.4%) compared to Group 2 (53.8% and 92.3%) and control (44.3% and 65.4%) eyes, respectively (P < 0.05). CONCLUSIONS: The use of IVT MTX injections in eyes with PVR undergoing RD repair was associated with a high rate of primary retinal attachment after SOR. Eyes that received IVT MTX injections after SOR had significantly lower rates of ERM and CME than eyes that did not.

10.
Polymers (Basel) ; 16(17)2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39274071

RESUMEN

For probing the structure-property relationships of the polyurea elastomers, we synthesize the siloxane polyurea copolymer elastomer by using two aminopropyl-terminated polysiloxane monomers with low and high number-average molecular weight (Mn), i.e., L-30D and H-130D. To study the influence of the copolymer structures on the film properties, these films are analyzed to obtain the tensile performance, UV-vis spectra, cross-sectional topographies, and glass transition temperature (Tg). The two synthetic thermoplastic elastomer films are characterized by transparency, ductility, and the Tg of the hard domains, depending on the reacting compositions. Furthermore, the film elasticity behavior is studied by the strain recovery and cyclic tensile test, and then, the linear fitting of the tensile data is used to describe the film elasticity based on the Mooney-Rivlin model. Moreover, the temperature-dependent infrared (IR) spectra during heating and cooling are conducted to study the strength and recovery rate of the hydrogen bonding, respectively, and their influence on the film performance is further analyzed; the calculated Mn of the hard segment chains is correlated to the macroscopic recovery rate of the hydrogen bonding. These results can add deep insight to the structure-property relationships of the siloxane polyurea copolymer.

11.
Sports Health ; : 19417381241277804, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39279244

RESUMEN

BACKGROUND: Despite growing applications of backward walking (BW) in assessing and rehabilitating neuromuscular conditions, its effects on gait in chronic ankle instability (CAI) remain unclear. Moreover, linking patient-reported and clinically generated measures is imperative for understanding CAI. HYPOTHESES: Patients with CAI will exhibit worse and compensatory spatio-temporal and kinetic gait parameters during BW, and patient-reported outcomes (PROs) will be correlated significantly with gait parameters. STUDY DESIGN: Case-control study. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 46 volunteers participated (23 per group). Patients filled out scales for pain, functions, and fear-avoidance beliefs before testing. All participants walked 6 times each in both forward and backward conditions, and gait was recorded using the Win-Track system. A 2-way mixed analysis of variance was performed to compare gait parameters. The relationship between PRO and gait outcomes was assessed through the Pearson product correlation coefficient. RESULTS: The CAI group demonstrated prolonged support and swing phases, increased walk-off angle, and plantar pressure area, but decreased step length and plantar pressure versus controls (P < 0.05). The CAI group had a smaller right walk-off angle during BW than FW; the control group showed the opposite (P < 0.05). The left single stance duration was greater in the CAI group, while the right was not (P < 0.05). PRO correlated significantly with gait parameters, particularly spatial parameters (P < 0.05). CONCLUSION: The CAI group exhibited worse gait parameters during BW. The CAI group exhibited a characteristic compensatory gait pattern. Linking the self-reported scores provides a better representation of gait changes in CAI. CLINICAL RELEVANCE: These results suggest that BW may be an effective strategy for identifying and evaluating CAI. It may be feasible to apply BW to the rehabilitation of CAI.

12.
Heliyon ; 10(16): e36146, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39262990

RESUMEN

Background: Scutellariae radix (SR) is the dried root of Scutellaria baicalensis Georgi. It has a long history of ethnic medicinal use, traditionally recognized for its efficacy in clearing heat, drying dampness, eliminating fire, removing toxins , stopping bleeding and tranquilizing fetus to prevent miscarriage. Clinically, it is used to treat cold, fever, migraine, hand-foot-and-mouth diseases, liver cancer and inflammatory diseases. Purpose: The review aims to provide a comprehensive reference on the ethnobotanical uses, processing, phytochemistry, pharmacological effect, quality control and influence factors of biosynthesis for a deeper understanding of SR. Results and conclusion: A total of 210 isolated components have been reported in the literature, including flavonoids and their glycosides, phenylpropanoids, phenylethanoid glycosides, phenolic acids, volatile components, polysaccharides and others. The extract of SR and its main flavonoids such as baicalin, baicalein, wogonin, wogonoside, and scutellarin showed antioxidant, anti-inflammatory, anti-tumor, antiviral, hepatoprotective, and neuroprotective effects. However, further studies are required to elucidate its mechanisms of action and clinical applications. The pharmacodynamic evaluation based on traditional efficacy should be conducted. Although various analytical methods have been established for the quality control of SR, there are gaps in the research regarding efficacy-related quality markers and the development of quality control standards for its processed products. The regulatory mechanisms of flavonoids biosynthesis remain to be explored while the influence of environmental and transcription factors on the biosynthesis have been studied. In conclusion, SR is a promising herbal medicine with significant potential for future development.

13.
Pharmacol Res ; 208: 107372, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39182661

RESUMEN

Saccharomyces boulardii (Sb) is a probiotic yeast for the treatment of gastrointestinal disorders, including inflammatory bowel disease (IBD). Little is known about the modulatory capacity of the Sb in IBD. Here, we found that oral gavage of Sb supernatant (SbS) alleviated gut inflammation, protected the intestinal barrier, and reversed DSS-induced down-regulated activation of epidermal growth factor receptor (EGFR) in colitis. Mass spectrum analysis showed that thioredoxin (Trx) is one of the critical secreted soluble proteins participating in EGFR activation detected in SbS. Trx exerted an array of significant effects on anti-inflammatory activity, including alleviating inflammation, protecting gut barrier, suppressing apoptosis, as well as reducing oxidative stress. Mechanistically, Trx promoted EGFR ligand gene expression and transactivated EGFR in a concentration-dependent manner. EGFR kinase inhibitor could block Trx-mediated preventive effects of intestinal epithelial injury. Our data suggested that Sb-derived soluble protein Trx could serve as a potential prophylactic, as a novel postbiotic against colitis, which provides a new strategy for the precision prevention and treatment of IBD.


Asunto(s)
Receptores ErbB , Saccharomyces boulardii , Tiorredoxinas , Animales , Humanos , Masculino , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/tratamiento farmacológico , Colitis/patología , Sulfato de Dextran , Receptores ErbB/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Probióticos/uso terapéutico , Probióticos/farmacología , Tiorredoxinas/metabolismo , Tiorredoxinas/genética
14.
iScience ; 27(8): 110421, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39108719

RESUMEN

The Streptomyces antibiotic regulatory proteins (SARPs) are ubiquitously distributed transcription activators in Streptomyces and control antibiotics biosynthesis and morphological differentiation. However, the molecular mechanism behind SARP-dependent transcription initiation remains elusive. We here solve the cryo-EM structure of an AfsR-loading RNA polymerase (RNAP)-promoter intermediate complex (AfsR-RPi) including the Streptomyces coelicolor RNAP, a large SARP member AfsR, and its target promoter DNA that retains the upstream portion straight. The structure reveals that one dimeric N-terminal AfsR-SARP domain (AfsR-SARP) specifically engages with the same face of the AfsR-binding sites by the conserved DNA-binding domains (DBDs), replacing σHrdBR4 to bind the suboptimal -35 element, and shortens the spacer between the -10 and -35 elements. Notably, the AfsR-SARPs also recruit RNAP through extensively interacting with its conserved domains (ß flap, σHrdBR4, and αCTD). Thus, these macromolecular snapshots support a general model and provide valuable clues for SARP-dependent transcription activation in Streptomyces.

17.
Nucleic Acids Res ; 52(18): e86, 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39193913

RESUMEN

Microorganisms can produce a vast array of bioactive secondary metabolites, including DNA-intercalating agents like actinomycin D, doxorubicin, which hold great potential for cancer chemotherapy. However, discovering novel DNA-intercalating compounds remains challenging due to the limited sensitivity and specificity of conventional activity assays, which require large-scale fermentation and purification. Here, we introduced the single-molecule stretching assay (SMSA) directly to microbial cultures or extracts for discovering DNA-intercalating agents, even in trace amounts of microbial cultures (5 µl). We showed that the unique changes of dsDNA in contour length and overstretching transition enable the specific detection of intercalators from complex samples without the need for extensive purification. Applying force to dsDNA also enhanced the sensitivity by increasing both the binding affinity Ka and the quantity of ligands intercalation, thus allowing the detection of weak intercalators, which are often overlooked using traditional methods. We demonstrated the effectiveness of SMSA, identified two DNA intercalator-producing strains: Streptomyces tanashiensis and Talaromyces funiculosus, and isolated three DNA intercalators: medermycin, kalafungin and ligustrone B. Interestingly, both medermycin and kalafungin, classified as weak DNA intercalators (Ka ∼103 M-1), exhibited potent anti-cancer activity against HCT-116 cancer cells, with IC50 values of 52 ± 6 and 70 ± 7 nM, respectively.


Asunto(s)
ADN , Sustancias Intercalantes , Streptomyces , Sustancias Intercalantes/química , Sustancias Intercalantes/farmacología , ADN/química , Humanos , Streptomyces/genética , Streptomyces/metabolismo , Imagen Individual de Molécula/métodos
18.
BMJ Open ; 14(7): e081623, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38991669

RESUMEN

INTRODUCTION: Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%-6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy. METHODS AND ANALYSIS: This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committees of the Sixth People's Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073864.


Asunto(s)
Carvedilol , Hipertensión Portal , Cirrosis Hepática , Carvedilol/uso terapéutico , Carvedilol/farmacología , Humanos , Hipertensión Portal/tratamiento farmacológico , Hipertensión Portal/etiología , Cirrosis Hepática/complicaciones , Método Doble Ciego , China/epidemiología , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Antagonistas Adrenérgicos beta/uso terapéutico , Femenino , Hígado/efectos de los fármacos , Hígado/fisiopatología , Presión Portal/efectos de los fármacos , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/prevención & control , Diagnóstico por Imagen de Elasticidad , Adulto , Masculino
19.
J Inflamm Res ; 17: 5025-5037, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39081873

RESUMEN

Objective: This prospective study is to explore the role of specific circRNAs in predicting the development of bronchopulmonary dysplasia (BPD). Methods: From July 1, 2021 to December 1, 2021, peripheral blood samples were collected from 62 premature infants with gestational age (GA) ≤32 weeks on the 7th, 14th, and 28th day after birth. Then, on the 28th day, the included infants were divided into the BPD group and the non-BPD group according to the definition of BPD. Serum exosomal circRNAs from peripheral blood were identified, sequenced, and compared between the BPD and non-BPD groups at different time points. Specific differentially expressed circRNAs were further verified from another 42 enrolled premature infants (GA ≤32 weeks). The classical lung biological markers in serum were also measured simultaneously. Results: Hsa_circ_0001359 in serum exosomes showed continuous differential expression between the BPD group and the non-BPD group on the 7th, 14th, and 28th day. Compared with that, classical lung biological markers like IL-6, IL-33, KL-6, and ET-1 did not exhibit continuous differences. Moreover, the expression of hsa_circ_0001359 on day 7 had a higher predictive value in predicting BPD (area under curve:0.853, 95% CI:0.738-0.968; adjusted odds ratio:6.033, 95% CI:2.373-13.326). The calibration curve further showed the mean absolute error = 0.033, mean squared error = 0.00231, and quantile of absolute error = 0.058. Conclusion: Hsa_circ_0001359 in serum exosomes is a promising marker for predicting BPD in preterm infants with gestational age ≤32 weeks.

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