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1.
Dis Colon Rectum ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39254197

RESUMEN

BACKGROUND: Continuous advancements and breakthroughs in flexible gastrointestinal endoscopy have led to alternatives to colonic anastomosis. OBJECTIVE: This study aimed to evaluate the feasibility and safety of end-to-end colonic anastomosis using a single flexible endoscope with the novel through-the-scope "bow-tie" (TTS-BT) device and conventional metal clips in a porcine model. DESIGN: Animal study. SETTINGS: Animal laboratory at China Medical University. PATIENTS: Eight healthy pigs were included. INTERVENTIONS: Eight animals underwent total colonic severance and anastomoses with through-the-scope "bow-tie" devices and metal clips. MAIN OUTCOME MEASURES: The primary outcomes were the success rate of the anastomosis and survival rate during 3-month follow-up. Furthermore, the secondary outcomes were anastomotic site healing, reintervention rate, and rate of anastomotic complications such as bleeding, leakage, stenosis, and obstruction. Six pigs were euthanized, and necropsies were performed 3 months postoperatively, while two pigs were fed for long-term observation. The anastomotic stoma was histologically analyzed using Hematoxylin-eosin and Masson's trichrome staining. RESULTS: End-to-end colonic anastomoses were successfully performed using through-the-scope "bow-tie" devices, and satisfactory healing was achieved in all pigs. The success rate of anastomosis was 100% (8/8). All animals survived postoperatively without anastomotic complications, including bleeding, leakage, or obstruction; however, two cases of stenosis occurred (25%), and one case (12.5%) required reintervention. LIMITATIONS: Large-scale studies should be conducted to verify the feasibility and safety of the through-the-scope "bow-tie" device in other parts of the intestine. CONCLUSIONS: Flexible endoscopy with the through-the-scope "bow-tie" device is feasible and safe for intraluminal colonic anastomosis. This study may expand the indications for full-thickness endoscopic resection in the future. See Video abstract.

2.
World J Gastroenterol ; 30(23): 2934-2946, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38946875

RESUMEN

In this editorial, we comment on an article titled "Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases", which was published in a recent issue of the World Journal of Gastroenterology. We focused on the statement that "autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal cells". With advancing research, autophagy, and particularly the pivotal role of the macroautophagy in maintaining cellular equilibrium and stress response in the gastrointestinal system, has garnered extensive study. However, the significance of mitophagy, a unique selective autophagy pathway with ubiquitin-dependent and independent variants, should not be overlooked. In recent decades, mitophagy has been shown to be closely related to the occurrence and development of gastrointestinal diseases, especially inflammatory bowel disease, gastric cancer, and colorectal cancer. The interplay between mitophagy and mitochondrial quality control is crucial for elucidating disease mechanisms, as well as for the development of novel treatment strategies. Exploring the pathogenesis behind gastrointestinal diseases and providing individualized and efficient treatment for patients are subjects we have been exploring. This article reviews the potential mechanism of mitophagy in gastrointestinal diseases with the hope of providing new ideas for diagnosis and treatment.


Asunto(s)
Autofagia , Enfermedades Gastrointestinales , Mitocondrias , Mitofagia , Humanos , Autofagia/fisiología , Enfermedades Gastrointestinales/patología , Enfermedades Gastrointestinales/metabolismo , Enfermedades Gastrointestinales/fisiopatología , Mitocondrias/metabolismo , Mitocondrias/patología , Tracto Gastrointestinal/patología , Tracto Gastrointestinal/metabolismo , Animales
3.
Endosc Ultrasound ; 13(2): 55-64, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38947746

RESUMEN

Rare malignant mesenchymal pancreatic tumors are systematized and reported in this review. The focus is on the appearance on imaging. The present overview summarizes the data and shows that not every pancreatic tumor corresponds to the most common entities of ductal adenocarcinoma or neuroendocrine tumor.

4.
Lancet Reg Health West Pac ; 48: 101122, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38993541

RESUMEN

Background: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) in the FURLONG study. Here we present prespecified secondary endpoints of patient-reported outcomes (PRO). Methods: In this multicentre, double-blind, double-dummy, randomised phase 3 study, patients were 1:1 randomly assigned to receive furmonertinib 80 mg once daily or gefitinib 250 mg once daily. PROs assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and Quality-of-Life Questionnaire Lung Cancer 13 were analysed using a mixed model for repeated measures and time-to-event analyses. A difference in score of 10 points or more was deemed clinically relevant. Findings: Three hundred and fifty-seven patients (furmonertinib group, n = 178; gefitinib group, n = 179) received at least one dose of the study drug, all of whom completed at least one PRO assessment. Statistically significant difference of overall score changes from baseline favoured furmonertinib in physical functioning (between-group difference 2.14 [95% CI 0.25-4.04], p = 0.027), nausea/vomiting (-1.56 [95% CI -2.62 to -0.49], p = 0.004), appetite loss (-2.24 [95% CI -4.26 to -0.23], p = 0.029), diarrhoea (-3.36 [95% CI -5.19 to -1.54], p < 0.001), alopecia (-2.62 [95% CI -4.54 to -0.71], p = 0.007), and pain in other parts (-4.55 [95% CI -7.37 to -1.74], p = 0.002), but not reached clinical relevance. Time to deterioration in physical functioning (hazard ratio 0.63 [95% CI 0.42-0.94], p = 0.021), cognitive functioning (0.73 [95% CI 0.54-0.98], p = 0.034), nausea/vomiting (0.64 [95% CI 0.41-0.99], p = 0.042), appetite loss (0.63 [95% CI 0.43-0.92], p = 0.016), diarrhoea (0.63 [95% CI 0.46-0.85], p = 0.002), dyspnoea (0.72 [95% CI 0.53-0.98], p = 0.034), cough (0.67 [95% CI 0.44-1.00], p = 0.049), dysphagia (0.54 [95% CI 0.35-0.83], p = 0.004), and alopecia (0.62 [95% CI 0.42-0.90], p = 0.012) was longer with furmonertinib versus gefitinib. Interpretation: In patients with locally advanced or metastatic EGFR mutation-positive NSCLC, furmonertinib showed improved scores and delayed deterioration in several functioning and symptoms compared to gefitinib. Funding: Shanghai Allist Pharmaceutical Technology Co., Ltd and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

5.
Gastrointest Endosc ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38734256

RESUMEN

BACKGROUND AND AIM: After endoscopic full-thickness resection (EFTR), defects require a reliable and sustained closure. We present a novel, through-the-scope "bow-tie" (TTS-BT) closing device enabling direct defect closure without scope withdrawal. This preclinical study aimed to evaluate the feasibility and safety of this device for large defect closure after EFTR in a porcine model. METHODS: Exposed EFTR was performed for virtual lesions > 2 cm in the stomach of twelve pigs. Subsequently, TTS-BT closing devices were used for defect closure. Conventional metal clips were used to close any remaining defects. Gastroscopy was performed for 8 weeks to examine the wound sites and the pigs were subsequently sacrificed. After sacrificing the pigs, the wound healing was histologically verified by hematoxylin-eosin (HE) staining. The primary outcome was a successful closure rate, while the secondary outcomes were complete healing rate, closure time, and incidence of adverse events. RESULTS: The median long and short diameters of perforations were 4.0 (3.0-6.0) cm and 3.0 (2.0-4.0) cm, respectively. Defect closure using novel TTS-BT closure devices and conventional metal clips was successfully performed in all pigs. Complete healing was achieved in the defects of 12 pigs. The median closure time was 13 (9-38) minutes. No serious adverse events occurred during the 8-week follow-up. CONCLUSIONS: The novel TTS-BT closure device is feasible and safe for closing large gastric perforations and could be a promising tool for clinical practice.

6.
Int J Surg ; 110(4): 2085-2091, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38668660

RESUMEN

BACKGROUND: The diagnostic ability of endoscopic ultrasound (EUS) for intestinal infiltration by pelvic masses has aroused considerable interest in many oncological settings. This study aimed to evaluate the effectiveness of EUS in predicting colorectal invasion in patients with pelvic masses and compare its accuracy with that of other imaging methods, namely pelvic MRI and abdominal computed tomography (CT), in predicting intestinal involvement in patients with histologically confirmed colorectal invasion. METHODS: A hundred and eighty-four female patients with histologically confirmed benign or malignant pelvic masses were enrolled in a retrospective-prospective study. All patients underwent EUS, pelvic MRI, and one or more of abdominal CT, transvaginal sonography, and colonoscopy examinations before surgery. The surgical and pathological results were used as the gold standard to evaluate the diagnostic accuracy of EUS for colorectal invasion of pelvic masses. RESULTS: This study included 184 patients who underwent surgery, with the time between EUS and surgery ranging from 1 to 309 (mean, 13.2) days. The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of EUS for benign and malignant pelvic masses infiltrating the intestine were 83.3, 97.8, 99.1, and 66.2%, respectively. The overall diagnostic accuracy was 87.0%. CONCLUSIONS: EUS is a simple, noninvasive, reliable, and accurate technique for the preoperative diagnosis of pelvic masses infiltrating the intestine. The authors recommend the use of this technology by gynecologists, as well as its incorporation into the preoperative diagnostic process to determine the most suitable surgical method. This would help in avoiding unexpected situations and unnecessary resource wastage during surgery.


Asunto(s)
Endosonografía , Humanos , Femenino , Endosonografía/métodos , Persona de Mediana Edad , Adulto , Anciano , Estudios Retrospectivos , Neoplasias Pélvicas/diagnóstico por imagen , Estudios Prospectivos , Anciano de 80 o más Años , Sensibilidad y Especificidad , Adulto Joven , Invasividad Neoplásica/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Imagen por Resonancia Magnética
7.
World J Gastrointest Endosc ; 16(3): 117-125, 2024 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-38577648

RESUMEN

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a means to procure adequate specimens for histological and cytologic analysis. The ideal EUS-FNA should be safe, accurate, and have a high sample adequacy rate and low adverse events rate. In recent years, many guidelines and trials on EUS-FNA have been published. The purpose of this article is to provide an update on the influence of some of the main factors on the diagnostic efficiency of EUS-FNA as well as a rare but serious complication known as needle tract seeding.

8.
World J Gastroenterol ; 30(9): 999-1004, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38577181

RESUMEN

The albumin-bilirubin (ALBI) score, which was proposed to assess the prognosis of patients with hepatocellular carcinoma, has gradually been extended to other liver diseases in recent years, including primary biliary cholangitis, liver cirrhosis, hepatitis, liver transplantation, and liver injury. The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models. It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators. An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease; additionally, it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases, such as decompensation events. This article presents a review of the application of ALBI scores in various non-malignant liver diseases.


Asunto(s)
Carcinoma Hepatocelular , Enfermedad Hepática en Estado Terminal , Neoplasias Hepáticas , Humanos , Bilirrubina , Albúmina Sérica , Enfermedad Hepática en Estado Terminal/diagnóstico , Enfermedad Hepática en Estado Terminal/cirugía , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Carcinoma Hepatocelular/patología , Pronóstico , Neoplasias Hepáticas/patología
9.
Front Oncol ; 13: 1247763, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38074676

RESUMEN

Background: Endoscopic ultrasound-guided biliary drainage (EUS-BD) is an alternative to endoscopic retrograde cholangiopancreatography (ERCP) for patients with obstructive jaundice. However, it is still a challenge for many endoscopists because of its novelty and complexity. This study aimed to establish an ideal bile duct dilatation model for the training and practice of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS). Methods: The 34 healthy Bama miniature pigs were divided into the part of developing the standardized EUS-CDS (n=9) and the part of trainees training (n=25). Part one, two different methods were used to clip Vater's ampulla using metal clips to establish an extrahepatic bile duct dilatation model. Part two, five trainees were trained on EUS-CDS with 25 pigs. Following a 2-week observation period, the feasibility and effectiveness of the technique were evaluated. Results: In the group with three metal clips perpendicular to the duodenal wall clipping Vater's ampulla, the success rate of extrahepatic bile duct dilation greater than 1 cm in 24 h was 5/6, whereas the remaining one pig was 48 h. All five trainees can finally complete the EUS-CDS independently. No death occurred during the 2-week observation period. Conclusion: Clipping Vater's ampulla with three metal clips perpendicular to the duodenal wall is an effective and stable method to create a porcine bile duct dilatation model.

10.
Ann Med ; 55(2): 2295991, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38134890

RESUMEN

Aim: Groove pancreatitis (GP) is a rare type of chronic pancreatitis characterized by varying degrees of thickening and scarring of the duodenal wall, duodenal lumen stenosis, mucosal hypertrophy with plicae and cyst formation. GP is primarily observed in middle-aged male patients with a history of alcohol consumption. Clinical symptoms are usually non-specific, and there is currently no unified diagnostic standard. However, imaging methods, particularly endoscopic ultrasound (EUS), are useful for diagnosis. EUS-guided biopsy can provide a strong basis for the final diagnosis. This review summarizes the value of EUS and its derivative technologies in the diagnosis, differential diagnosis and treatment of GP.Methods: After searching in PubMed and Web of Science databases using 'groove pancreatitis (GP)' and 'endoscopic ultrasonography (EUS)' as keywords, studies related were compiled and examined.Results: EUS and its derivative technologies are of great significance in the diagnosis, differential diagnosis, and treatment of GP, but there are still limitations that need to be comprehensively applied with other diagnostic methods to obtain the most accurate results.Conclusion: EUS has unique value in both the diagnosis and treatment of GP. Clinicians need to be well-versed in the advantages and limitations of EUS for GP diagnosis to select the most suitable imaging diagnostic method for different cases and to reduce the unnecessary waste of medical resources.


Asunto(s)
Endosonografía , Pancreatitis Crónica , Persona de Mediana Edad , Humanos , Masculino , Pancreatitis Crónica/diagnóstico por imagen , Biopsia
11.
Ann Med ; 55(2): 2282748, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37967551

RESUMEN

Aim: The lumen-apposing metal stent (LAMS) is a new device that expands the scope of gastrointestinal intervention under endoscopy. LAMS was initially used for the treatment of pancreatic fluid collections (PFCs), but is increasingly being used off-label. The electrocautery system simplifies the deployment of LAMS, making it more suitable for off-label situations. The short-term results of electrocautery-enhanced lumen-apposing metal stents (ECE-LAMS) are satisfactory; however, the long-term follow-up results must be evaluated. The aim of this article is to review the expanded clinical application of ECE-LAMS, the clinical value of on-label and off-label use, and follow-up results.Methods: After searching in PubMed and Web of Science databases using 'electrocautery-enhanced lumen-apposing metal stents' and 'endoscopic ultrasonography (EUS) -guided interventions' as keywords, studies related were compiled and examined.Results: ECE-LAMS are widely used for on-label and off-label situations. The short-term and long-term results of ECE-LAMS are satisfactory, but there are still some studies that do not agree with this viewpoint.Conclusion: The clinical application of ECE-LAMS is relatively safe and reliable but more well-designed randomized trials and prospective studies are needed to evaluate the impact of this technology on therapeutic EUS, to improve the safety and success rate of EUS-guided LAMS implantation, and to expand its application in other indications.


Asunto(s)
Drenaje , Endosonografía , Humanos , Endosonografía/métodos , Estudios de Seguimiento , Drenaje/métodos , Stents , Electrocoagulación/métodos , Resultado del Tratamiento
12.
Ann Med ; 55(2): 2281656, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37949085

RESUMEN

The vascular and morphological features of tumors are important predictors of the nature, grade, and stage of various cancers. However, this association has not been tested in bladder cancer. The aim of our study was to investigate the correlation between the morphological characteristics of tumor vessels and the nature, stage and grade of bladder cancer. Between November 2021 and March 2023, we prospectively collated clinical information and cystoscopy information from a series of patients with bladder cancer. Univariate and multivariate logistic regression analysis were used to identify independent risk factors for the nature, grade and stage of bladder cancer. Our analysis showed that cauliflower-like tumors, dotted vessels, and circumferential vessels were independent risk factors for bladder cancer. Reticular vessels were an independent risk factor for high-grade bladder cancer. Thick branching vessels in bladder tumors, along with a wide base, were independent risk factors for the invasion of bladder cancer into the lamina propria. Primary diagnosis, lesion location (beside the left ureteral orifice) and obscure lesion boundaries were all identified as independent risk factors for muscle invasive bladder cancer.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Humanos , Estudios Prospectivos , Estadificación de Neoplasias , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/patología , Cistoscopía/métodos , Factores de Riesgo
13.
Free Radic Biol Med ; 209(Pt 1): 1-8, 2023 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-37802373

RESUMEN

Several studies have indicated that reactive oxygen species (ROS) can lead to detrusor overactivity (DO), but the underlying mechanisms are not known. Hydrogen dioxide (H2O2) is used commonly to investigate the effects of ROS. In present study, we investigated the effects of H2O2 on phasic spontaneous bladder contractions (SBCs) of isolated human-bladder strips (iHBSs) and the underlying mechanisms. Samples of bladder tissue were obtained from 26 patients undergoing cystectomy owing to bladder cancer. SBCs of iHBSs were recorded in organ-bath experiments. H2O2 (1µM-10mM) concentration-dependently increased the SBCs of iHBSs. These enhancing effects could be mimicked by an agonist of transient receptor potential (TRP)A1 channels (allyl isothiocyanate) and blocked with an antagonist of TRPA1 channels (HC030031; 10 µM). H2O2 induced enhancing effects also could be attenuated by desensitizing sensory afferents with capsaicin (10 µM), blocking nerve firing with TTX (1 µM), blocking neurokinin effects with NK2 receptor antagonist (SR48968, 10 µM), and blocking PGE2 synthesis with indomethacin (10 µM), respectively. Our study: (i) suggests activation of TRPA1 channels on bladder sensory afferents, and then release of substance P or PGE2 from sensory nerve terminals, contribute to the H2O2-induced enhancing effects on SBCs of iHBSs; (ii) provides insights for the mechanisms underlying ROS leading to DO; (iii) indicates that targeting TRPA1 channels might be the promising strategy against overactive bladder in conditions associated with excessive production of ROS.


Asunto(s)
Canales de Potencial de Receptor Transitorio , Vejiga Urinaria , Humanos , Vejiga Urinaria/inervación , Vejiga Urinaria/fisiología , Sustancia P/farmacología , Peróxido de Hidrógeno/farmacología , Dinoprostona , Especies Reactivas de Oxígeno/metabolismo , Canal Catiónico TRPA1/genética
14.
J Cancer Res Clin Oncol ; 149(17): 15867-15877, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37672077

RESUMEN

PURPOSE: At present, the prediction of bladder tumor nature during cystoscopy is partially dependent on the clinician's own experience. Subjective factors may lead to excessive biopsy or delayed treatment. The purpose of our study is to establish a reliable model for predicting the nature of bladder tumors using narrow band imaging. METHODS: From November 2021 to November 2022, the clinical data of 231 patients who required a cystoscopy were prospectively collected at our center. Cystoscopy was performed in 219 eligible patients, in which both tumor and vascular morphology characteristics were recorded. Pathological results were used as the diagnostic standard. A logistic regression analysis was used to screen out factors related to tumor pathology. Bootstrap resampling was used for internal validation. A total of 71 patients from four other centers served as an external validation cohort. RESULTS: The following diagnostic factors were identified: tumor morphology (cauliflower-like or algae-like lesions), vascular morphology (dotted or circumferential vessels), tumor boundary (clear or unclear), and patients' symptoms (gross hematuria) and were included in the prediction model. The internal validation results showed that the area under the curve was 0.94 (95% CI 0.92-0.97), and the P value from the goodness-of-fit test was 0.97. After external validation, the results showed the area under the curve was 0.89 (95% CI 0.82-0.97) and the P value of the goodness-of-fit test was 0.24. CONCLUSION: A diagnostic prediction nomogram was established for bladder cancer. The verification results showed that the prediction model has good prediction performance.


Asunto(s)
Imagen de Banda Estrecha , Neoplasias de la Vejiga Urinaria , Humanos , Imagen de Banda Estrecha/métodos , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/patología , Nomogramas , Cistoscopía/métodos , Estudios Retrospectivos
15.
Int J Mol Sci ; 24(11)2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37298451

RESUMEN

The activation of the transient receptor potential ankyrin 1 (TRPA1) channel has anti-fibrotic effects in the lung and intestine. Suburothelial myofibroblasts (subu-MyoFBs), a specialized subset of fibroblasts in the bladder, are known to express TRPA1. However, the role of the TRPA1 in the development of bladder fibrosis remains elusive. In this study, we use the transforming growth factor-ß1 (TGF-ß1) to induce fibrotic changes in subu-MyoFBs and assess the consequences of TRPA1 activation utilizing RT-qPCR, western blotting, and immunocytochemistry. TGF-ß1 stimulation increased α-SMA, collagen type I alpha 1 chain(col1A1), collagen type III (col III), and fibronectin expression, while simultaneously suppressing TRPA1 in cultured human subu-MyoFBs. The activation of TRPA1, with its specific agonist allylisothiocyanate (AITC), inhibited TGF-ß1-induced fibrotic changes, and part of these inhibition effects could be reversed by the TRPA1 antagonist, HC030031, or by reducing TRPA1 expression via RNA interference. Furthermore, AITC reduced spinal cord injury-induced fibrotic bladder changes in a rat model. The increased expression of TGF-ß1, α-SMA, col1A1 and col III, and fibronectin, and the downregulation of TRPA1, were also detected in the mucosa of fibrotic human bladders. These findings suggest that TRPA1 plays a pivotal role in bladder fibrosis, and the negative cross talk between TRPA1 and TGF-ß1 signaling may represent one of the mechanisms underlying fibrotic bladder lesions.


Asunto(s)
Fibronectinas , Miofibroblastos , Animales , Humanos , Ratas , Colágeno Tipo III/metabolismo , Fibroblastos/metabolismo , Fibronectinas/metabolismo , Fibrosis , Miofibroblastos/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Canal Catiónico TRPA1/genética , Canal Catiónico TRPA1/metabolismo , Vejiga Urinaria/patología
16.
Aging Dis ; 14(5): 1677-1699, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37196111

RESUMEN

The novel COVID-19 pneumonia caused by the SARS-CoV-2 virus poses a significant threat to human health. Scientists have made significant efforts to control this virus, consequently leading to the development of novel research methods. Traditional animal and 2D cell line models might not be suitable for large-scale applications in SARS-CoV-2 research owing to their limitations. As an emerging modelling method, organoids have been applied in the study of various diseases. Their advantages include their ability to closely mirror human physiology, ease of cultivation, low cost, and high reliability; thus, they are considered to be a suitable choice to further the research on SARS-CoV-2. During the course of various studies, SARS-CoV-2 was shown to infect a variety of organoid models, exhibiting changes similar to those observed in humans. This review summarises the various organoid models used in SARS-CoV-2 research, revealing the molecular mechanisms of viral infection and exploring the drug screening tests and vaccine research that have relied on organoid models, hence illustrating the role of organoids in remodelling SARS-CoV-2 research.

17.
Mol Neurobiol ; 60(9): 5000-5012, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37227654

RESUMEN

Mechanical sensing Piezo2 channel in primary sensory neurons has been shown contribute to mechanical allodynia in somatic chronic pain conditions. Interstitial cystitis (IC)-associated pain is often triggered by bladder filling, a presentation that mimics the mechanical allodynia. In the present study, we aimed to examine the involvement of sensory Piezo2 channel in IC-associated mechanical allodynia using a commonly employed cyclophosphamide (CYP)-induced IC model rat. Piezo2 channels in dorsal root ganglia (DRGs) was knocked down by intrathecal injections of Piezo2 anti-sense oligodeoxynucleotides (ODNs) in CYP-induced cystitis rats, and mechanical stimulation-evoked referred bladder pain was measured in the lower abdomen overlying the bladder using von Frey filaments. Piezo2 expression at the mRNA, protein, and functional levels in DRG neurons innervating the bladder was detected by RNA-fluorescence in situ hybridization, western blotting, immunofluorescence, and Ca2+ imaging, respectively. We found that Piezo2 channels were expressed on most (> 90%) of the bladder primary afferents, including afferents that express CGRP, TRPV1 and stained with isolectin B4. CYP-induced cystitis was associated with Piezo2 upregulation in bladder afferent neurons at the mRNA, protein, and functional levels. Knockdown of Piezo2 expression in DRG neurons significantly suppressed mechanical stimulation-evoked referred bladder pain as well as bladder hyperactivity in CYP rats compared to CYP rats treated with mismatched ODNs. Our results suggest upregulation of Piezo2 channels is involved in the development of bladder mechanical allodynia and bladder hyperactivity in CYP-induced cystitis. Targeting Piezo2 might be an attractive therapeutic approach for IC-related bladder pain.


Asunto(s)
Cistitis , Hiperalgesia , Ratas , Animales , Hiperalgesia/metabolismo , Regulación hacia Arriba , Hibridación Fluorescente in Situ , Cistitis/complicaciones , Cistitis/inducido químicamente , Cistitis/metabolismo , Ciclofosfamida/efectos adversos , Dolor/complicaciones , ARN Mensajero/genética , ARN Mensajero/metabolismo
18.
Therap Adv Gastroenterol ; 16: 17562848231163414, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37153498

RESUMEN

Benign and malignant pelvic masses with or without intestinal invasion are common in women of childbearing age. Patients may have nonspecific symptoms and signs or experience no symptoms. Laparoscopic resection of pelvic masses is currently the mainstream treatment; therefore, accurate preoperative evaluation is not only essential for patients suspected of having intestinal invasion, but also extremely important for the selection of follow-up treatment. Procedures, including endoscopic ultrasonography (EUS), pelvic magnetic resonance imaging, abdominal computed tomography, vaginal ultrasonography, barium enema, and colonoscopy, aid in determining the presence, depth, and histology of the disease. In particular, the wide application and continuous developments in EUS techniques have improved the diagnostic accuracy for intestinal subepithelial and peripheral organ lesions. This article reviewed the clinical value of EUS in the diagnosis of benign and malignant pelvic masses with bowel involvement.

19.
BMC Med ; 21(1): 164, 2023 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-37118803

RESUMEN

BACKGROUND: Furmonertinib (AST2818) is a brain penetrant pan-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting both EGFR sensitizing mutations and T790M mutation. We report the pooled central nervous system (CNS) efficacy data of furmonertinib in patients with EGFR T790M mutated non-small cell lung cancer (NSCLC) from two phase 2 studies. METHODS: This was a pooled, post-hoc analysis of two phase 2 studies (NCT03127449 [phase 2a study of furmonertinib], NCT03452592 [phase 2b study of furmonertinib]). In the phase 2a study, patients received furmonertinib 40 mg, 80 mg, 160 mg, or 240 mg orally once daily. In the phase 2b study, all patients received furmonertinib 80 mg orally once daily. CNS efficacy of furmonertinib was analyzed in patients with baseline CNS lesions by an independent review center per Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: A total of 132 patients with baseline CNS metastases were included in this analysis. In 52 patients with measurable CNS lesions, CNS objective response rates were zero (0/1), 65% (22/34), 85% (11/13), and 25% (1/4), and CNS disease control rates were zero (0/1), 97% (33/34), 100% (13/13), and 100% (4/4) in the 40 mg, 80 mg, 160 mg, and 240 mg orally once daily group, respectively. In patients with measurable or non-measurable CNS lesions, median CNS progression-free survival was 2.8 months (95% confidence interval [CI] 1.4-8.3), 11.6 months (95% CI 8.3-13.8), 19.3 months (95% CI 5.5-not available [NA]), and not reached (95% CI 2.8 months-NA) in the 40 mg, 80 mg, 160 mg, and 240 mg orally once daily group, respectively. CONCLUSIONS: Furmonertinib showed promising CNS efficacy in doses of 80 mg orally once daily or higher in patients with EGFR T790M mutated NSCLC. TRIAL REGISTRATION: Both studies were registered on ClinicalTrial.gov. The phase 2a study was registered with NCT03127449 on April 25, 2017; The phase 2b study was registered with NCT03452592 on March 2, 2018.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Receptores ErbB/genética , Inhibidores de Proteínas Quinasas/efectos adversos , Mutación , Sistema Nervioso Central/patología , Ensayos Clínicos Fase II como Asunto
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