Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 260
Filtrar
1.
Cell Death Dis ; 13(1): 56, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35027539

RESUMO

Circular RNAs (circRNAs) play a vital role in the occurrence and development of tumors, including gastric cancer (GC). However, there are still many circRNAs related to GC whose functions and molecular mechanisms remain undetermined. Herein, we discover circRNA RELL1, which has not been investigated in GC, and it is markedly downregulated in GC tissues, which is related with poor prognosis, more pronounced lymph node metastasis and poor TNM stage. After confirming the circular structure of circRELL1, we found that circRELL1 could block cell proliferation, invasion, migration, and anti-apoptosis in patients with GC by a series of in vivo and in vitro function-related studies. Further mechanism investigation demonstrated that circRELL1 could sponge miR-637 and indirectly unregulated the expression of EPHB3 via modulating autophagy activation in GC. Additionally, circRELL1 can be transmitted by exosomal communication, and exosomal circRELL1 suppressed the malignant behavior of GC in vivo and in vitro. Taken together, this study elucidates the suppressive roles of circRELL1/miR-637/EPHB3 axis through autophagy activation in GC progression, inspiring for further understanding of the underlying molecular mechanisms of GC and providing a promising novel diagnostic circulating biomarker and therapeutic target in GC.

3.
Chem Commun (Camb) ; 58(4): 557-560, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34908047

RESUMO

We developed a simple method to fabricate a strongly coupled Fe-doped NiS2/MoS2 composite by introducing dual confinement effects during the vapor vulcanization of precursors, which involves the controlled release of metal species and the in situ formation of an N-doped carbon layer. The Fe-doped NiS2/MoS2 composite exhibited a much-enhanced hydrogen/oxygen evolution reaction performance.

4.
Cancer Control ; 28: 10732748211063955, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34913741

RESUMO

BACKGROUND: The number of patients diagnosed with T1 stage adenocarcinoma of esophagogastric junction (AEGJ) has been increasing. This study was conducted to investigate the effect of different treatment options (surgery, chemoradiation, and surgery+chemoradiation) on long-term survival in patients with T1-stage AEGJ. METHODS: We searched the Surveillance, Epidemiology, and End Results (SEER) database to identify the records of patients with T1-stage AEGJ between 2010 and 2018. Patient demographics and cancer parameters were compared among the three groups. The Kaplan-Meier method and Cox proportional hazard modeling were used to compare long-term survival. RESULTS: Data from 925 T1 stage AEGJ patients (surgery: n=516, surgery+chemoradiation: n=206, chemoradiation: n=203) were collected. We found that the OS and CSS rates of three treatment options had significant difference. Besides, positive nodal status also showed lower OS and CSS rat. Multivariate Cox regression analysis showed that surgery group has much lower risk of death compared with chemoradiation group and similar risk of death compared with surgery+chemoradiation group. Subgroup analysis suggested that in patients with N1-N3 status had higher OS and CSS rates in surgery+chemoradiation group. CONCLUSION: Using SEER data, we identified a significant survival advantage with the use of surgery compared to chemoradiation in patients with T1-stage AEGJ while the long-term survival of patients after surgery+chemoradiation group was not significantly different and low risk of death in positive nodal status.

5.
Gut ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34836916

RESUMO

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

6.
Int J Biol Sci ; 17(15): 4165-4175, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803490

RESUMO

Background: Inflammation and apoptosis play a crucial role in the progression of nonalcoholic steatohepatitis (NASH). Suppressor of cytokine signaling 2 (SOCS2) is one of classic negative regulators of cytokine signaling, which has recently been described as anti-inflammatory mediators. However, the role of SOCS2 in macrophages during NASH progression and the relationship among SOCS2, inflammation, apoptosis and NASH is largely unknown. Herein, we aimed to study the function of SOCS2 in NASH progression. Methods: We detected SOCS2 expression in macrophages in human subjects without steatosis, with simple steatosis and with NASH to confirm the relationship between SOCS2 and NASH. Free fatty acids was used to establish stress environment in RAW 264.7 cell lines stably overexpressing or knockdown SOCS2. In vitro and vivo assays also performed to study the molecular function of SOCS2 in NASH progression. Findings: Our human samples illustrated that SOCS2 was decreased in macrophages during NASH progression and was negatively correlated to NASH level. Meanwhile, In vitro assays showed SOCS2 overexpression in macrophages suppressed inflammation and apoptosis via inhibiting NF-κB signaling pathway, while SOCS2 knock-down in macrophages caused an increased activation of NF-κB, which could be blocked by ammonium 1-pyrrolidinedithiocarbamate (PDTC). In addition, SOCS2 in macrophages also suppressed inflammation via limiting the activation of inflammasomes. Consistent with these, our BMT model also confirmed the SOCS2 function in macrophages during NASH. Interpretation: Our data strongly indicate that SOCS2 plays a role in inhibiting inflammation and apoptosis via NF-κB and inflammasome signaling pathway in macrophages during NASH. Further studies are required to explore the potential preventive and therapeutic strategies of SOCS2 for this common liver disease.

7.
Surg Endosc ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34792629

RESUMO

BACKGROUND AND AIM: Endoscopic closure of chronic gastrointestinal fistulas (CGFs) is challenging due to their epithelialized surfaces. The aim of this study was to assess the efficacy and long-term closure rate of endosuturing for CGFs with an Apollo Overstitch device. PATIENTS AND METHODS: Consecutive CGF patients undergoing endosuturing for fistula closure from April 2018 to January 2020 at the First Affiliated Hospital of Nanjing Medical University were enrolled for retrospective review. Demographics, fistula characteristics, details of the suturing procedures and outcomes were collected for analysis. RESULTS: Twenty patients (mean age 59.8 ± 9.1 years; 85% males) with a total of 23 CGFs underwent sutured fistula closure. Esophagotracheal fistulas were the most common CGFs (12/23, 52.2%), and prior cancer surgery was the most common fistulization etiology (14/20, 70%). Twelve patients (12/20, 60%) had undergone failed endoscopic attempts at fistula closure before suturing. Additional endoscopic therapies used during suturing were 100% argon plasma coagulation, 50% clip fixation, and 10% stent placement. Although all patients undergoing suturing achieved immediate technical success of fistula closure, sustained fistula closure was observed in only 5 patients (5/20, 25.0%) on surveillance endoscopy 3 months after suturing with a mean follow-up of 19.5 months. Esophagotracheal fistula patients were predisposed to shorter dehiscence-free survival than those with other fistulas (HR 3.378; 95% CI 1.127-10.13). CONCLUSIONS: Endosuturing is safe and should be considered for use as the first-line or salvage therapy for CGF closure, primarily for patients with fistulas not involving the trachea. However, the long-term healing of CGFs by suturing is challenging, and CGF patients might not benefit from repeated suturing.

8.
Cancer Discov ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615656

RESUMO

Glioblastoma (GBM) is the most lethal primary brain cancer characterized by therapeutic resistance, which is promoted by GBM stem cells (GSCs). Here, we interrogated gene expression and whole genome CRISPR/Cas9 screening in a large panel of patient-derived GSCs, differentiated glioblastoma cells (DGCs), and neural stem cells (NSCs) to identify master regulators of GSC stemness, revealing an essential transcription state with increased RNA polymerase II-mediated transcription. The YY1 and transcriptional CDK9 complex was essential for GSC survival and maintenance in vitro and in vivo. YY1 interacted with CDK9 to regulate transcription elongation in GSCs. Genetic or pharmacological targeting of YY1-CDK9 complex elicited RNA m6A modification-dependent interferon responses, reduced regulatory T cell infiltration, and augmented efficacy of immune checkpoint therapy in glioblastoma. Collectively, these results suggest that YY1-CDK9 transcription elongation complex defines a targetable cell state with active transcription, suppressed interferon responses, and immunotherapy resistance in glioblastoma.

9.
J Exp Med ; 218(11)2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34617969

RESUMO

Glioblastoma ranks among the most lethal of primary brain malignancies, with glioblastoma stem cells (GSCs) at the apex of tumor cellular hierarchies. Here, to discover novel therapeutic GSC targets, we interrogated gene expression profiles from GSCs, differentiated glioblastoma cells (DGCs), and neural stem cells (NSCs), revealing EYA2 as preferentially expressed by GSCs. Targeting EYA2 impaired GSC maintenance and induced cell cycle arrest, apoptosis, and loss of self-renewal. EYA2 displayed novel localization to centrosomes in GSCs, and EYA2 tyrosine (Tyr) phosphatase activity was essential for proper mitotic spindle assembly and survival of GSCs. Inhibition of the EYA2 Tyr phosphatase activity, via genetic or pharmacological means, mimicked EYA2 loss in GSCs in vitro and extended the survival of tumor-bearing mice. Supporting the clinical relevance of these findings, EYA2 portends poor patient prognosis in glioblastoma. Collectively, our data indicate that EYA2 phosphatase function plays selective critical roles in the growth and survival of GSCs, potentially offering a high therapeutic index for EYA2 inhibitors.

10.
J Biomed Res ; 35(5): 361-370, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34628403

RESUMO

Superficial esophageal squamous cell carcinoma (SESCC) is defined as carcinoma with mucosal or submucosal invasion, regardless of regional lymph node metastasis (LNM). The lymph node status is not only a key factor to determine the training strategy, but also the most important prognostic factor in esophageal cancer. In this study, we establish a clinical nomogram for predicting LNM in patients with SESCC. A predictive model was established based on the training cohort composed of 711 patients who underwent esophagectomy for SESCC from December 2009 to June 2018. A prospective cohort of 203 patients from June 2018 to January 2019 was used for validation. Favorable calibration and well-fitted decision curve analysis were conducted and good discrimination was observed (concordance index [C-index], 0.860; 95% confidence interval [CI], 0.825-0.894) through internal validation. The external validation cohort presented good discrimination (C-index, 0.916; 95% CI, 0.860-0.971). This model may facilitate the prediction of LNM in patients with SESCCs.

11.
Int J Phytoremediation ; : 1-13, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34651532

RESUMO

The plants Feicai (Sedum aizoon L.) and dandelion(Taraxacum mongolicum Hand.-Mazz.) have good salt tolerance, and can improve soil quality and the micro-ecological environment. Coastal saline-soil plots planted with S. aizoon and T. mongolicum and bare plots were used to explore their effects on the microbial community structure of coastal saline soil. The diversity and function of soil bacterial communities were analyzed using Illumina MiSeq high-throughput sequencing technology. The results showed that the α-diversity of soil bacterial communities were higher in planted than in bare plots, in the following order: T. mongolicum plot > S. aizoon plot > bare plot. The soil bacterial communities also changed after planting S. aizoon and T. mongolicum. The LDA effect size analysis showed that there were 37 indicator species among the three plot types. Correlation analysis of environmental factors showed that EC, AP, and OM were the main factors influencing bacterial community composition in this coastal saline soil. The PICRUSt functional prediction showed that the numbers of metabolic functions of bacterial communities were in the following order: T. mongolicum plot > S. aizoon plot > bare plot. The results provide a theoretical basis and plant species for developing salt-tolerant bacterial resources and phytoremediation of coastal saline soil.

12.
Nanoscale ; 13(42): 17890-17899, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34673874

RESUMO

The distinct structure and maximum utilization of metal atoms on supported single-atom catalysts (SACs) represents a new frontier of heterogeneous catalysis, yet the low-cost mass production of high-performance SACs is still a key issue for practical applications. Herein, by coating a formamide-derived highly N-modified carbonaceous layer as a "glue" on commercially available activated carbon black (AC), a hundred-gram scale synthesis of atomically dispersed non-noble metal-nitrogen-carbon (MNC) materials was realized, including but not limited to Fe, Co, Ni, Mn, and Cu. The dispersion and coordination environments of Fe atoms on AC were initially revealed by XRD, HRTEM, and XPS, and further confirmed by HAADF-STEM and XANES analysis, presenting Fe atoms in a Fe-N4 structure. The atomically dispersed metal species, though relatively low-loading grafted on AC (typical loading of 0.16 to 0.29 at%), are mostly distributed on the electrochemically accessible surface, resulting in improved metal utilization. The FeNC@AC-3 sample exhibited highly comparable catalytic performance to 20 wt% Pt/C for the alkaline oxygen reduction reaction, and superior Al-air battery performance. Our work may inspire the synthesis of other types of SACs for broad electrocatalysis applications at kilogram or even ton scale.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34547790

RESUMO

BACKGROUND: Considering the complexity of lung structures and the difficulty of thoracoscopic surgery, simulation-based training is of paramount importance for junior surgeons. Here, we aim to design a high-fidelity lung model through utilizing the three-dimensional (3D) printing technology combined with synthetic materials to mimic the real human lung. METHODS: The 3D printed lung model was manufactured based on the computed tomography images of a randomly selected male patient. Synthetic materials were used for the construction of lung parenchyma, blood vessels, and bronchi. Then, the model was assessed in terms of its visual, tactile, and operational features by participants (the senior surgeons, junior surgeons, and medical students), who were asked to complete the specially designed survey-questionnaires. RESULTS: A 3D printed model of the right lung made of synthetic materials was successfully fabricated. Thirty subjects participated in our study (10 senior surgeons, 10 junior surgeons, and 10 medical students). The average visual evaluation scores for senior surgeons, junior surgeons, and medical students were 3.97 ± 0.61, 4.56 ± 0.58, 4.76 ± 0.49, respectively. The average tactile evaluation scores were 3.40 ± 0.50, 4.13 ± 0.68, 4.00 ± 0.64, respectively. The average operation evaluation scores were 3.33 ± 0.83, 3.93 ± 0.66, 4.03 ± 0.66, respectively. Significant lower scores were obtained in the group of the senior surgeons compared with the other two groups. CONCLUSION: A high level of fidelity was exhibited in our 3D printed lung model and it could be applied as a promising simulator for the surgical training in the future.

14.
Mol Ther Nucleic Acids ; 26: 360-373, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34552818

RESUMO

Circular (circ)RNAs are widely involved in gastric cancer (GC) pathogenesis, and coiled-coil domain containing 6 (CCDC6) is a fused partner of multiple oncogenes; however, the underlying mechanisms of how circRNAs regulate CCDC6 expression in the progression and prognosis of GC remain unclear. Here, we discovered the circRNA derived from the DNA2 gene locus (circDNA2) through RNA sequencing. By performing quantitative real-time PCR and fluorescence in situ hybridization (FISH) assays with a human tissue microarray, circDNA2 was found to be highly expressed in GC tissues and associated with lymphatic invasion of GC patients. Knockdown of circDNA2 expression suppressed the proliferation of GC cells by reducing CCDC6 expression. Mechanistically, circDNA2 acted as a microRNA (miR)-149-5p sponge, which was confirmed to target CCDC6 by RNA pulldown and dual-luciferase reporter assays and rescue experiments. Both low miR-149-5p expression and high CCDC6 expression were related to unfavorable prognosis in GC patients. Moreover, GC patients with low miR-149-5p expression had shorter overall survival and a higher risk of chemotherapy resistance than those with high miR-149-5p expression. In summary, circDNA2 contributes to the growth and lymphatic metastasis of GC by upregulating CCDC6 expression by sponging miR-149-5p. The circDNA2/miR-149-5p/CCDC6 axis might be developed as a therapeutic target and prognostic indicator for GC.

15.
Materials (Basel) ; 14(18)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34576526

RESUMO

The advancement of 3D printing and scanning technology enables the digitalization and customization of foot orthosis with better accuracy. However, customized insoles require rectification to direct control and/or correct foot deformity, particularly flatfoot. In this exploratory study, we aimed at two design rectification features (arch stiffness and arch height) using three sets of customized 3D-printed arch support insoles (R+U+, R+U-, and R-U+). The arch support stiffness could be with or without reinforcement (R+/-) and the arch height may or may not have an additional elevation, undercutting (U+/-), which were compared to the control (no insole). Ten collegiate participants (four males and six females) with flexible flatfoot were recruited for gait analysis on foot kinematics, vertical ground reaction force, and plantar pressure parameters. A randomized crossover trial was conducted on the four conditions and analyzed using the Friedman test with pairwise Wilcoxon signed-rank test. Compared to the control, there were significant increases in peak ankle dorsiflexion and peak pressure at the medial midfoot region, accompanied by a significant reduction in peak pressure at the hindfoot region for the insole conditions. In addition, the insoles tended to control hindfoot eversion and forefoot abduction though the effects were not significant. An insole with stronger support features (R+U+) did not necessarily produce more favorable outcomes, probably due to over-cutting or impingement. The outcome of this study provides additional data to assist the design rectification process. Future studies should consider a larger sample size with stratified flatfoot features and covariating ankle flexibility while incorporating more design features, particularly medial insole postings.

16.
J BUON ; 26(4): 1239-1245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34564976

RESUMO

PURPOSE: The purpose of this study was to research and validate techniques for extracting DNA from human genomes, explore the sensitivity and specificity of known nucleic acid markers of intestinal malignancy in Chinese patients with early colorectal cancer. We also tried to find adenoma-specific biomarkers in human DNA in feces. METHODS: We compared the ability of fecal DNA testing, Fecal Occult Blood Testing (FOBT) and serum tumor markers to diagnose different types of polyps, and DNA testing was significantly superior to the other two methods. We also found a dominant expression of NDRG12b methylation in multi-target DNA testing, which may be a promising marker for detection of colorectal precancerosis. RESULTS: The sensitivity of NDRG4 12b methylation was 85.7% for advanced adenomatous polyp (AP), and 62.6% for non-advanced AP, respectively, with specificity of 70.8%. The diagnostic efficacy of NDRG4 12b methylation for detecting advanced AP was significantly higher than FOBT (sesitivity: 85.7% vs. 42.9%, p<0.05). The receiver operating characteristics (ROC) curve for NDRG4 12b methylation in detecting AP showed a relatively high area under the curve (AUC = 0.807). CONCLUSIONS: Our results indicate that highly sensitive fecal DNA testing of NDRG4 12b methylation is a promising marker for detection of colorectal precancerosis, especially in detecting adenomatous polyp.

17.
Comput Methods Programs Biomed ; 211: 106408, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34537493

RESUMO

BACKGROUND AND OBJECTIVE: Mid/hindfoot arthrodesis could modify the misalignment of adult-acquired flatfoot and attenuate pain. However, the long-term biomechanical effects of these surgical procedures remain unclear, and the quantitative evidence is scarce. Therefore, we aimed to investigate and quantify the influences of five mid/hindfoot arthrodeses on the internal foot biomechanics during walking stance. METHODS: A young participant with flexible flatfoot was recruited for this study. We reconstructed a subject-specific musculoskeletal multibody driven-finite element (FE) foot model based on the foot magnetic resonance imaging. The severe flatfoot model was developed from the flexible flatfoot through the attenuation of ligaments and the unloading of the posterior tibial muscle. The five mid/hindfoot arthrodeses simulations (subtalar, talonavicular, calcaneocuboid, double, and triple arthrodeses) and a control condition (no arthrodesis) were performed simultaneously in the detailed foot multibody dynamics model and FE model. Muscle forces calculated by a detailed multi-segment foot model and ground reaction force were used to drive the foot FE model. The internal foot loadings were compared among control and these arthrodeses conditions at the first and second vertical ground reaction force (VGRF) peak and VGRF valley instants. RESULTS: The results indicated that the navicular heights in double and triple arthrodeses were higher than other surgical procedures, while the subtalar arthrodesis had the smallest values. Five mid/hindfoot arthrodeses reduced the peak plantar fascia stress compared to control. However, double and triple arthrodeses increased the peak medial cuneo-navicular joint contact pressures and peak foot pressures as well as the metatarsal bones stresses. CONCLUSION: Although mid/hindfoot arthrodesis generally reduced the collapse of medial longitudinal arch and plantar fascia loading during the stance phase, the increased loading in the adjacent unfused joint and metatarsal bones for double and triple arthrodeses should be noted. These findings could account for some symptoms experienced by flatfoot patients after surgery, which may facilitate the optimization of surgical protocols.


Assuntos
Pé Chato , Adulto , Artrodese , Fenômenos Biomecânicos , Análise de Elementos Finitos , Pé Chato/cirurgia , , Humanos
18.
J Cancer ; 12(19): 5789-5796, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475992

RESUMO

Background: Widespread endoscopic submucosal dissection (ESD) in early esophageal cancer patients is closely associated with esophageal stricture, which dramatically reduces patients' quality of life and increases huge medical burdens. Endoscopic injection of steroid was proved as a protective method for post-ESD strictures. Other materials such as botulinum toxin type A (BTX-A) may be potential candidates. We conducted this prospective cohort study to compare the efficacy and feasibility of endoscopic injection of BTX-A and triamcinolone acetonide (TA) for the prevention of esophageal stricture. Methods: Seventy-eight patients with esophageal mucosal defects of more than two thirds of the circumference were successively enrolled and divided into 3 groups: BTX-A group (group A, n=26), TA group (group B, n=16) and control group (group C, n=36). Patients in group A were immediately injected with BTX-A after ESD, in group B were immediately injected with TA and in group C received ESD only. Endoscopy was performed when patients reported dysphagia symptoms and at 6 and 12 weeks post-ESD in patients without symptoms. Patients who experienced post-ESD esophageal strictures in all groups received bougie dilation. All patients were followed up for one year. Results: The proportion of patients developing stricture in BTX-A group was 30.00% (intention to treat analysis, 9/30) and 26.92% (per protocol analysis, 7/26), in TA group was 40.90% (intention to treat analysis, 9/22) and 43.75% (per protocol analysis, 7/16), and in control group was 84.21% (intention to treat analysis, 32/38) and 83.33% (per protocol analysis, 30/36) (p<0.001). When further comparing between each of the two groups, the incidence of esophageal stricture was lower in BTX-A group than that in control group (p<0.001), and lower in TA group than that in control group (p=0.004). Furthermore, in entire circumference mucosal defect subgroup, the esophageal stricture was significantly lower in BTX-A group than that in TA group (33.3% vs 100%, p=0.0454). Conclusions: Endoscopic injection of BTX-A and TA were effective in preventing post-ESD esophageal strictures and BTX-A injection was particularly effective in entire circumference mucosal defect patients. Multi-centered, randomized prospective study with larger sample size should be conducted. (Clinical trial registration number: ChiCTR2100042970, registered 1 February 2021, retrospectively registered, http://www.chictr.org.cn/listbycreater.aspx).

19.
Front Med (Lausanne) ; 8: 690995, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336894

RESUMO

Background: Proton pump inhibitors (PPIs) are validated gastric acid suppressors and have been widely used to treat patients with active duodenal ulcers. Although existing PPIs have shown great efficacy, many scientists are still devoted to developing more effective PPIs with better safety profile. Herein, we aimed to compare the safety and efficacy of anaprazole in duodenal mucosal healing, a novel PPI, to that of rabeprazole. Methods: In this multicenter, randomized, positive-controlled, double-blinded, parallel-group phase II clinical trial, a total of 150 qualified patients with endoscopically confirmed active duodenal ulcers were randomized (1:1:1) to receive rabeprazole 10 mg, anaprazole 20 mg or anaprazole 40 mg for 4 weeks. The ulcer healing rates after 4 weeks of treatment were compared between groups by independent central review and investigator review. In addition, symptoms and safety were evaluated. Results: Based on the independent central review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole and 40 mg anaprazole groups were 88.0, 85.1, and 87.5%, respectively, in the FAS population and 88.9, 86.0, and 90.9%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is -2.9% (95% CI, -16.5-10.7%), and -0.5% (95% CI, -13.5-12.5%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Based on the investigator review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole, and 40 mg anaprazole groups were 72.0, 70.2, and 77.1%, respectively, in the FAS population and 75.6, 72.1, and 79.5%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is -1.8% (95% CI, -19.8-16.3%), and 5.1% (95% CI, -12.2-22.3%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Most patients (>90%) eventually achieved complete symptom relief. The incidence rates of adverse events were of no significant differences among the treatment groups. Potential possible better liver tolerance was observed in two anaprazole dose groups than rabeprazole 10 mg group. Conclusion: Both at a dosage of 20 and 40 mg daily, anaprazole, is effective with good safety profile in the treatment of active duodenal ulcers in this Phase 2 study, which allows anaprazole to be advanced to a phase III clinical trial. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/results?cond=&term=NCT04503629&cntry=&state=&city=&dist=, Identifier: CTR20181464, NCT04503629.

20.
Front Oncol ; 11: 683465, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422636

RESUMO

Purpose: Gastric cancer (GC) is often difficult to diagnose early in the disease and remains one of the most frequently occurring malignancies. This investigation looks at the diagnostic potential of a specific plasma exosomal miRNAs panel for GC. Methods: This study analyzed 216 individual peripheral blood samples. 2 GEO datasets were analyzed and two miRNAs were selected - plasma exosomal miR-195-5p and miR-211-5p. Quantitative reverse-transcriptase PCR (qRT-PCR) was used to assess relative expressions and receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic efficiency of miR-195-5p and miR-211-5p panel. The Kaplan-Meier method was used to assess the prognostic value of plasma exosomal miR-195-5p and miR-211-5p. Results: GC patients possessed notably raised plasma levels of exosomal miR-195-5p and miR-211-5p. The area under ROC curves (AUCs) of miR-195-5p, miR-211-5p were 0.745, 0.798 in the screening phase and 0.762, 0.798 in the training stage respectively. GC was able to be diagnosed more accurately when both miRNAs were interpreted together (AUC=0.820 in the validation stage). Poorer prognosis was observed in GC patients who had plasma exosomal miR-195-5p and miR-211-5p of higher levels. In vitro experiments also confirmed that miR-195-5p and miR-211-5p is able to be transmitted between cells, and works to enhance tumor invasion, migration and proliferation while inhibiting cell apoptosis. Conclusion: Plasma exosomal miR-195-5p and miR-211-5p may become potential biomarkers for GC diagnosis, and may be useful in predicting tumor phenotype.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...