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Vitamins are dietary components necessary for cellular metabolic balance, especially redox homeostasis; deficient or excessive supply may give rise to symptoms of psychiatric disorders. Exploring the nutritional and metabolic pathways of vitamins could contribute to uncovering the underlying pathogenesis of ferroptosis-associated diseases. This mini-review aims to provide insights into vitamins closely linked to the regulation of ferroptosis from the perspective of cellular reactive oxygen species biology. The mainstream reprogramming mechanisms of ferroptosis are overviewed, focusing on unique biological processes of iron metabolism, lipid metabolism, and amino acid metabolism. Moreover, recent breakthroughs in therapeutic interventions targeting ferroptosis via fully utilizing vitamin-based pharmacological tools were overviewed, covering vitamins (B, C, E, and K). Finally, mechanism insight related to vitamin-associated nutrient signaling was provided, highlighting the pharmacological benefits of metabolically reprogramming ferroptosis-associated diseases.
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PURPOSE: To investigate the influencing factors of intraoperative hypothermia (IOH) in patients undergoing total joint arthroplasty (TJA) of the lower extremities, establish a risk prediction model, and test the effect of application. DESIGN: A prospective, observational study was conducted. METHODS: Patients who underwent total knee arthroplasty and total hip arthroplasty from June 2020 to December 2021 were prospectively analyzed. According to the occurrence of IOH, patients were divided into the IOH group (temperature less than 36 °C) and non-IOH group (temperature ≥36 °C). We collected demographic, anesthesia, and surgical data for both groups to identify risk factors for IOH and develop a predictive model. The model's goodness of fit was assessed using the Hosmer-Lemeshow test, and its predictive efficacy was evaluated using the receiver operating characteristic curve. FINDINGS: A total of 258 patients were included in this study, with 79 patients in the IOH group and 179 patients in the non-IOH group. Logistic regression analysis showed that American Society of Anesthesiologists' grade, blood loss, and duration of surgery were independent risk factors for IOH in lower extremity TJA patients. Hosmer-Lemeshow test P = .803, area under receiver operating characteristic curve was 0.846, Youden index was 0.490, sensitivity was 65.4%, specificity was 83.6%. In the external validation cohort, the application accuracy of the model was 83.3%. CONCLUSIONS: The prediction model established in this study is suitable for the risk assessment of IOH in TJA patients with good prediction effect, which can provide a tool for clinical medical staff to identify high-risk populations preoperatively.
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BACKGROUND AND AIMS: Gastric intestinal metaplasia is a precancerous disease, and a timely diagnosis is essential to delay or halt cancer progression. Artificial intelligence (AI) has found widespread application in the field of disease diagnosis. This study aimed to conduct a comprehensive evaluation of AI's diagnostic accuracy in detecting gastric intestinal metaplasia in endoscopy, compare it to endoscopists' ability, and explore the main factors affecting AI's performance. METHODS: The study followed the PRISMA-DTA guidelines, and the PubMed, Embase, Web of Science, Cochrane, and IEEE Xplore databases were searched to include relevant studies published by October 2023. We extracted the key features and experimental data of each study and combined the sensitivity and specificity metrics by meta-analysis. We then compared the diagnostic ability of the AI versus the endoscopists using the same test data. RESULTS: Twelve studies with 11,173 patients were included, demonstrating AI models' efficacy in diagnosing gastric intestinal metaplasia. The meta-analysis yielded a pooled sensitivity of 94% (95% confidence interval: 0.92-0.96) and specificity of 93% (95% confidence interval: 0.89-0.95). The combined area under the receiver operating characteristics curve was 0.97. The results of meta-regression and subgroup analysis showed that factors such as study design, endoscopy type, number of training images, and algorithm had a significant effect on the diagnostic performance of AI. The AI exhibited a higher diagnostic capacity than endoscopists (sensitivity: 95% vs. 79%). CONCLUSIONS: AI-aided diagnosis of gastric intestinal metaplasia using endoscopy showed high performance and clinical diagnostic value. However, further prospective studies are required to validate these findings.
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Inteligencia Artificial , Metaplasia , Humanos , Metaplasia/diagnóstico , Metaplasia/patología , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Sensibilidad y Especificidad , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Curva ROC , Estómago/patologíaRESUMEN
Bioretention facilities have proven highly effective in removing pollutants from runoff. However, there is a concerning paucity of research on the contamination characteristics and associated risks posed by refractory pollutants in these facilities following long-term operation. This research focuses on the distribution, sources, microbial community impact, and human health risks of pollutants in eight bioretention facilities that have been operational for 5-11 years. The results showed that the distribution of Cu, Zn, and Cd was closely related to anti-seepage measures. PAHs, PCBs, and OCPs primarily accumulated in the surface, with concentrations ranging from 7.42 to 20.34 mg/kg, 31.8-77.3 µg/kg, and 60.5-163.6 µg/kg, respectively. Their concentrations inversely correlate with the depth of the media. Although the majority of contaminants remained below their respective risk thresholds, their concentrations typically exceeded those of background soil values, indicating an enrichment phenomenon. Source analysis revealed that PAHs primarily originate from oil combustion, PCBs were linked to their related industrial products, DDTs had their main sources in technical DDx and residues from the use of dicofol, while HCHs were traced back to historical residues from agricultural activities. Microbial α-diversity (Chao 1 and Shannon) decreased by 8.3-23.4% and 0.8-4.4%, respectively, in different facilities after long-term operation. The most dominant microbial phylum in the facilities was Proteobacteria (all relative abundances >48%). The total relative abundance of dominant genera was 6.7-34.3% higher than the control site, and Pseudomonas, a typical POPs-heavy metal degrading bacterium, had the highest relative abundance (>1.2%). Cu, Zn, and Cd present no non-carcinogenic risks and have low potential ecological risks. However, the lifetime cancer risk for PAHs is 10-6 â¼10-4 in most facilities and is of concern. The cancer risk for PCBs is acceptable, while OCPs pose a low cancer risk only for children.
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Metales Pesados , Contaminantes Orgánicos Persistentes , Medición de Riesgo , Metales Pesados/análisis , Humanos , Monitoreo del Ambiente , Contaminantes del Suelo/análisis , MicrobiotaRESUMEN
Artificial dissipative molecular switches based on anion recognition are of great importance to simulate biological functions and construct smart materials. Five activated carboxylic acids are used as chemical fuels for dissipative molecular switches, which consist of an imidazolium macrocyclic host and a carboxylate anionic guest. By choosing different types of chemical fuels and using varied fuel concentrations, the rates of cyclic operations are tunable. The operation is capable of undergoing at least three cycles.
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Objective: Adalimumab (ADA) is an effective treatment for inflammatory bowel disease (IBD), both ulcerative colitis (UC) and Crohn's disease (CD). The equal effect between the original ADA and biosimilars from Europe and the United States has been shown. However, the biosimilar of ADA is different in China. The effectiveness and safety data of ADA biosimilar (HS016) in China have yet to be discovered. Patients and methods: 91 patients (75 CD, 16 UC) received HS016 treatment and were enrolled in this study. Therapeutic response and safety profiles were analyzed. Therapeutic drug monitoring (TDM) was also carried out among nonresponse patients. After being considered as "nonresponse" (after three or 6 months of treatment), 20 patients' serum TNFα concentrations were measured and correlated to their disease severity. Results: Among active CD patients (n = 61), 75.4% (46/61) at 12 w, 73.8% (45/61) at 26 w, 50.8% (31/61) at 52 w achieved the clinical response, respectively; 55.7% (34/61) at 12 w, 65.6% (40/61) at 26 w, and 45.9% (28/61) at 52 w achieved clinical remission. The maintained remission rates of CD (n = 14) in clinical remission were 100% (14/14) at 12 w, 78.6% (11/14) at 26 w, and 63.6% (7/11) at 52 w, respectively. Among active UC patients, 37.5% (6/16) at 12 w and 50% (8/16) at 26 w achieved clinical response. Total adverse event rates were 5.5% (5/91) during 52-week visits. Due to the inadequate serum drug concentration, 30.4% (7/23) of patients had poor clinical responses. Elevations of serum anti-drug antibodies occurred in one additional patient (4.3%). Conclusion: ADA biosimilar HS016 had good efficacy and safety in Chinese IBD patients.
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The pandemic of COVID-19 was a major public health events and had a deeply impact on the healthcare acquired by patients with inflammatory bowel disease (IBD). The purpose of this study was to evaluate the long-term impacts on healthcare service in Chinese IBD patients under the dynamic zero-COVID strategy. The study was performed in the Inflammatory Bowel Disease Quality of Care Centers in mainland China in 2021. The data about the healthcare was collected by a 44-item questionnaire. Totally 463 were from ulcerative colitis (UC) patients and 538 from Crohn's disease (CD) patients were included in the study. The pandemic impacted 37.5% patients on their treatment, and the biggest problem was unable to follow up timely (77.9%). There was a significant increase in healthcare costs in CD (P < 0.001) and no significant change in UC (P = 0.14) after the outbreak. Both UC and CD had an increase in the frequency of outpatient visits (UC 5.07 vs. 4.54, P = 0.001; CD 6.30 vs. 5.76, P = 0.002), and hospitalizations (UC 1.30 vs. 1.02, P < 0.001; CD 3.55 vs. 2.78, P < 0.001). The hospitalization rate in UC reduced slightly (40.2% vs. 42.8%, P = 0.423) after the outbreak, but it significantly increased in CD (75.8% vs. 67.8%, P = 0.004). The rate of biologics had significant increased (UC 11.2% vs. 17.7%, P = 0.005; CD 53.2% vs. 71.0%, P < 0.001). Besides, the proportion of people using telemedicine also increased from 41.6% to 55.1% (P < 0.001). However, 82.8% patients still preferred face-to-face visits. Recurrent outbreaks and the regular pandemic prevention and control policy had a long-term impact on medical care service for IBD patients. The preferred mode of healthcare was still face-to-face visit. It will be a long way to go in the construction of telemedicine in China.
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Colitis Ulcerosa , Enfermedad de Crohn , Atención a la Salud , Enfermedades Inflamatorias del Intestino , Humanos , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/epidemiología , Estudios Transversales , Pueblos del Este de Asia , Costos de la Atención en Salud , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/terapia , Pandemias , COVID-19RESUMEN
Endoscopic remission is an important therapeutic goal in ulcerative colitis (UC). The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Mayo Endoscopic Score (MES) are the commonly used endoscopic scoring criteria. This systematic review and meta-analysis aimed to evaluate the accuracy of artificial intelligence (AI) in diagnosing endoscopic remission in UC. We also performed a meta-analysis of each of the four endoscopic remission criteria (UCEIS = 0, MES = 0, UCEIS = <1, MES = <1). Eighteen studies involving 13,687 patients were included. The combined sensitivity and specificity of AI for diagnosing endoscopic remission in UC was 87% (95% confidence interval [CI]:81-92%) and 92% (95% CI: 89-94%), respectively. The area under the curve (AUC) was 0.96 (95% CI: 0.94-0.97). The results showed that the AI model performed well regardless of which criteria were used to define endoscopic remission of UC.
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Bioretention facilities are one of the most widely used measures for urban stormwater control and utilization. In this study, the accumulation characteristics of polycyclic aromatic hydrocarbons (PAHs) in bioretention facilities and the effects of PAHs on the structure of microbial communities were explored by combining on-site monitoring and water distribution simulation experiments. The correlation between pollutant accumulation and dominant microorganisms in the bioretention systems was also clarified. The results showed that all 16 priority PAHs were detected in the bioretention facilities in the sponge city pilot area. The PAH concentrations in the soil during the non-rainy season were higher than those in the rainy season and medium- and high-ring PAHs dominated. PAHs in the study area were mainly derived from coal and biomass combustion. The potential carcinogenic risk of PAHs accumulated in the bioretention facilities in the study area was low. The microbial diversity during the non-rainy season was greater than that during the rainy season. Firmicutes, Bacteroidetes, Bacteroides, and Massilia were strongly correlated with naphthalene (NAP), pyrene (PYR), fluoranthene (FLT), and benzo[a]pyrene (BaP). According to the results of the small-scale water distribution test, the addition of PAHs had little effect on the decline in water quantity, and there was no significant regularity in the reduction of water quality including TP, NH4+-N, NO3-N, and TN. The addition of PAHs had a significant effect on the microbial community structure and an inhibitory effect on enzyme activity.
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Contaminantes Ambientales , Microbiota , Hidrocarburos Policíclicos Aromáticos , Hidrocarburos Policíclicos Aromáticos/análisis , Carcinógenos/análisis , Suelo/química , Monitoreo del Ambiente , China , Medición de RiesgoRESUMEN
Background and aims: Endoscopic ultrasonography (EUS) is commonly utilized in the diagnosis of pancreatic tumors, although as this modality relies primarily on the practitioner's visual judgment, it is prone to result in a missed diagnosis or misdiagnosis due to inexperience, fatigue, or distraction. Deep learning (DL) techniques, which can be used to automatically extract detailed imaging features from images, have been increasingly beneficial in the field of medical image-based assisted diagnosis. The present systematic review included a meta-analysis aimed at evaluating the accuracy of DL-assisted EUS for the diagnosis of pancreatic tumors diagnosis. Methods: We performed a comprehensive search for all studies relevant to EUS and DL in the following four databases, from their inception through February 2023: PubMed, Embase, Web of Science, and the Cochrane Library. Target studies were strictly screened based on specific inclusion and exclusion criteria, after which we performed a meta-analysis using Stata 16.0 to assess the diagnostic ability of DL and compare it with that of EUS practitioners. Any sources of heterogeneity were explored using subgroup and meta-regression analyses. Results: A total of 10 studies, involving 3,529 patients and 34,773 training images, were included in the present meta-analysis. The pooled sensitivity was 93% (95% confidence interval [CI], 87-96%), the pooled specificity was 95% (95% CI, 89-98%), and the area under the summary receiver operating characteristic curve (AUC) was 0.98 (95% CI, 0.96-0.99). Conclusion: DL-assisted EUS has a high accuracy and clinical applicability for diagnosing pancreatic tumors. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023391853, identifier CRD42023391853.
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Objective: Behçet's Disease (BD) is an intractable systemic vasculitis. When accompanied by intestinal symptoms, the prognosis is usually poor. 5-Aminosalicylic acid (5-ASA), corticosteroids, immunosuppressive drugs, and anti-tumor necrosis factor-α (anti-TNF-α) biologics are standard therapies to induce or maintain remission for intestinal BD. However, they might not be effective in refractory cases. Safety should also be considered when patients have an oncology history. Regarding the pathogenesis of intestinal BD and the specific targeting effect of vedolizumab (VDZ) on the inflammation of the ileum tract, previous case reports suggested that VDZ might be a potential treatment for refractory intestinal BD. Methods: We report a 50-year-old woman patient with intestinal BD who had oral and genital ulcers, joint pain, and intestinal involvement for about 20 years. The patient responds well to anti-TNF-α biologics but not to conventional drugs. However, biologics treatment was discontinued due to the occurrence of colon cancer. Results: VDZ was intravenously administered at a dose of 300 mg at 0, 2, and 6 weeks and then every eight weeks. At the 6-month follow-up, the patient reported significant improvement in abdominal pain and arthralgia. We observed complete healing of intestinal mucosal ulcers under endoscopy. However, her oral and vulvar ulcers remained unresolved, which disappeared after adding thalidomide. Conclusion: VDZ may be a safe and effective option for refractory intestinal BD patients who do not respond well to conventional treatments, especially those with an oncology history.
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Síndrome de Behçet , Productos Biológicos , Enfermedades Intestinales , Humanos , Femenino , Persona de Mediana Edad , Síndrome de Behçet/complicaciones , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Úlcera/tratamiento farmacológico , Úlcera/etiología , Factor de Necrosis Tumoral alfa/uso terapéutico , Factores Biológicos/uso terapéutico , Productos Biológicos/uso terapéuticoRESUMEN
Background and aims: The diagnosis of chronic atrophic gastritis (CAG) under normal white-light endoscopy depends on the endoscopist's experience and is not ideal. Artificial intelligence (AI) is increasingly used to diagnose diseases with good results. This review aimed to evaluate the accuracy of AI-assisted diagnosis of CAG through a meta-analysis. Methods: We conducted a comprehensive literature search of four databases: PubMed, Embase, Web of Science, and the Cochrane Library. Studies published by November 21, 2022, on AI diagnosis CAG with endoscopic images or videos were included. We assessed the diagnostic performance of AI using meta-analysis, explored the sources of heterogeneity through subgroup analysis and meta-regression, and compared the accuracy of AI and endoscopists in diagnosing CAG. Results: Eight studies that included a total of 25,216 patients of interest, 84,678 image training set images, and 10,937 test set images/videos were included. The results of the meta-analysis showed that the sensitivity of AI in identifying CAG was 94% (95% confidence interval [CI]: 0.88-0.97, I2 = 96.2%), the specificity was 96% (95% CI: 0.88-0.98, I2 = 98.04%), and the area under the summary receiver operating characteristic curve was 0.98 (95% CI: 0.96-0.99). The accuracy of AI in diagnosing CAG was significantly higher than that of endoscopists. Conclusions: AI-assisted diagnosis of CAG in endoscopy has high accuracy and clinical diagnostic value. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42023391853.
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BACKGROUND: Ustekinumab (UST) is an IL12/23 inhibitor utilized for altering inflammatory responses in inflammatory bowel disease (IBD). Clinical trials and case reports suggested that the effectiveness and safety of UST may differ among IBD patients in Eastern and Western countries. However, related data have not been systematically reviewed and analyzed. METHODS: This systematic review and meta-analysis of the safety and effectiveness of UST in IBD included relevant literature from the Medline and Embase databases. The main outcomes were clinical response, clinical remission, endoscopic response, endoscopic remission, and adverse events in IBD. RESULTS: We analyzed 49 real-world studies, most of which included patients with biological failure (89.1% CD and 97.1% UC). In UC patients, clinical remission rates were 34% at 12 weeks, 40% at 24 weeks, and 37% at 1 year. In CD patients, clinical remission rates were 46% at 12 weeks, 51% at 24 weeks, and 47% at 1 year. Clinical remission rates of CD patients were 40% at 12 weeks and 44% at 24 weeks in Western countries, versus 63% and 72% in Eastern countries, respectively. CONCLUSION: UST is an effective drug for IBD with a promising safety profile. Although no RCTs have been performed in Eastern countries, the effectiveness of UST on CD patients is not inferior to that in Western countries based on the existing data.
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Background: Chronic atrophic gastritis (CAG) is a precancerous condition. It is not easy to detect CAG in endoscopy. Improving the detection rate of CAG under endoscopy is essential to reduce or interrupt the occurrence of gastric cancer. This study aimed to construct a deep learning (DL) model for CAG recognition based on endoscopic images to improve the CAG detection rate during endoscopy. Methods: We collected 10,961 endoscopic images and 118 video clips from 4,050 patients. For model training and testing, we divided them into two groups based on the pathological results: CAG and chronic non-atrophic gastritis (CNAG). We compared the performance of four state-of-the-art (SOTA) DL networks for CAG recognition and selected one of them for further improvement. The improved network was called GAM-EfficientNet. Finally, we compared GAM-EfficientNet with three endoscopists and analyzed the decision basis of the network in the form of heatmaps. Results: After fine-tuning and transfer learning, the sensitivity, specificity, and accuracy of GAM-EfficientNet reached 93%, 94%, and 93.5% in the external test set and 96.23%, 89.23%, and 92.37% in the video test set, respectively, which were higher than those of the three endoscopists. Conclusions: The CAG recognition model based on deep learning has high sensitivity and accuracy, and its performance is higher than that of endoscopists.
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Ferroptosis, a novel regulated cell death induced by iron-dependent lipid peroxidation, plays an important role in tumor development and drug resistance. Long noncoding RNAs (lncRNAs) are associated with various types of cancer. However, the precise roles of many lncRNAs in tumorigenesis remain elusive. Here we explored the transcriptomic profiles of lncRNAs in primary CRC tissues and corresponding paired adjacent non-tumor tissues by RNA-seq and found that LINC00239 was significantly overexpressed in colorectal cancer tissues. Abnormally high expression of LINC00239 predicts poorer survival and prognosis in colorectal cancer patients. Concurrently, we elucidated the role of LINC00239 as a tumor-promoting factor in CRC through in vitro functional studies and in vivo tumor xenograft models. Importantly, overexpression of LINC00239 decreased the anti-tumor activity of erastin and RSL3 by inhibiting ferroptosis. Collectively, these data suggest that LINC00239 plays a novel and indispensable role in ferroptosis by nucleotides 1-315 of LINC00239 to interact with the Kelch domain (Nrf2-binding site) of Keap1, inhibiting Nrf2 ubiquitination and increasing Nrf2 protein stability. Considering the recurrence and chemoresistance constitute the leading cause of death in colorectal cancer (CRC), ferroptosis induction may be a promising therapeutic strategy for CRC patients with low LINC00239 expression.
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Neoplasias Colorrectales , Ferroptosis , ARN Largo no Codificante , Neoplasias Colorrectales/patología , Ferroptosis/genética , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
DEAD-box helicase 27 (DDX27) was previously identified as an important mediator during carcinogenesis, while its role in gastric cancer (GC) is not yet fully elucidated. Here, we aimed to investigate the mechanism and clinical significance of DDX27 in GC. Public datasets were analyzed to determine DDX27 expression profiling. The qRT-PCR, Western blot, and immunohistochemistry analyses were employed to investigate the DDX27 expression in GC cell lines and clinical samples. The role of DDX27 in GC metastasis was explored in vitro and in vivo. Mass spectrometry, RNA-seq, and alternative splicing analysis were conducted to demonstrate the DDX27-mediated molecular mechanisms in GC. We discovered that DDX27 was highly expressed in GCs, and a high level of DDX27 indicated poor prognosis. An increased DDX27 expression could promote GC metastasis, while DDX27 knockdown impaired GC aggressiveness. Mechanically, the LLP expression was significantly altered after DDX27 downregulation, and further results indicated that LPP may be regulated by DDX27 via alternative splicing. In summary, our study indicated that DDX27 contributed to GC malignant progression via a prometastatic DDX27/LPP/EMT regulatory axis.
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BACKGROUND AND AIMS: Sec62 is a membrane protein of the endoplasmic reticulum that facilitates protein transport. Its role in cancer is increasingly recognised, but remains largely unknown. We investigated the functional role of Sec62 in gastric cancer (GC) and its underlying mechanism. METHODS: Bioinformatics, tissue microarray, immunohistochemistry (IHC), western blotting (WB), quantitative polymerase chain reaction (qPCR), and immunofluorescence were used to examine the expression of target genes. Transwell, scratch healing assays, and xenograft models were used to evaluate cell migration and invasion. Transmission electron microscopy and mRFP-GFP-LC3 double-labeled adenoviruses were used to monitor autophagy. Co-immunoprecipitation (CO-IP) was performed to evaluate the binding activity between the proteins. RESULTS: Sec62 expression was upregulated in GC, and Sec62 upregulation was an independent predictor of poor prognosis. Sec62 overexpression promoted GC cell migration and invasion both in vitro and in vivo. Sec62 promoted migration and invasion by affecting TIMP-1 and MMP2/9 balance. Moreover, Sec62 could activate autophagy by upregulating PERK/ATF4 expression and binding to LC3II with concomitant FIP200/Beclin-1/Atg5 activation. Furthermore, autophagy blockage impaired the promotive effects of Sec62 on GC cell migration and invasion, whereas autophagy activation rescued the inhibitory effect of Sec62 knockdown on GC metastasis. Notably, Sec62 inhibition combined with autophagy blockage exerted a synergetic anti-metastatic effect in vitro and in vivo. CONCLUSION: Sec62 promotes GC metastasis by activating autophagy and subsequently regulating TIMP-1 and MMP2/9 balance. The activation of autophagy by Sec62 may involve the unfolded protein response (UPR)-related PERK/ATF4 pathway and binding of LC3II during UPR recovery involving FIP200/Beclin-1/Atg5 upregulation. Specifically, the dual inhibition of Sec62 and autophagy may provide a promising therapeutic strategy for GC metastasis.
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Autofagia/fisiología , Proteínas de Transporte de Membrana/fisiología , Neoplasias Gástricas/patología , Respuesta de Proteína Desplegada/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Línea Celular Tumoral , Femenino , Humanos , Hidroxicloroquina/farmacología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Neoplasias Gástricas/mortalidad , Inhibidor Tisular de Metaloproteinasa-1/fisiología , eIF-2 Quinasa/genéticaRESUMEN
BACKGROUND: In the past 3 years, increasing data and experience has become available regarding fecal microbiota transplantation (FMT) for the treatment of inflammatory bowel disease (IBD). However, how this increase in knowledge has impacted the attitudes of patients and physicians is largely unknown. This study aimed to investigate the change of patients' and physicians' attitudes towards FMT for IBD treatment. METHODS: Questionnaires for patient and physician attitude on FMT for IBD were pilot-tested and developed. Patients and physicians from the same groups completed the questionnaires in 2016 and 2019, separately. The attitudes towards efficacy, adverse events, and methodological features of FMT in 2016 were compared with those in 2019. RESULTS: A total of 1,255 questionnaires from 486 patients and 769 physicians were collected. Over the 3 years, an increased number of patients had heard of FMT and had similarly positive opinions towards using FMT for IBD therapy. Additionally, patients retained the tendency to overestimate the efficacy. The physicians' perceptions became closer to the findings reported in recent studies in 2019 compared with 2016. However, only a minority of patients and physicians understood the frequency required of FMT courses for induction of clinical remission. In particular, both patients and physicians underestimated the risk of mild adverse events and IBD flare. CONCLUSIONS: Patients are receptive towards FMT as therapy for IBD but opportunity remains to improve understanding of benefit and potential risks. Physicians also demonstrated knowledge gaps in use of this therapy. Aligning patient preference and physician knowledge gap will lead to better education and facilitate the development of decision-making guidelines.
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Purpose: To evaluate the efficacy and tolerability of adjunctive perampanel (PER) in Chinese patients with focal-onset seizures, with or without secondarily generalized tonic-clonic seizures. Methods: Fifty-six patients aged 14-72 years were recruited consecutively in this single-center prospective observational study. All patients received PER as add-on treatment on the basis of clinical judgment. Seizure frequency, adverse events (AEs), and retention rates were obtained at 3 and 6 months after PER introduction. Results: The overall response rates were 60 and 71.1% after 3 and 6 months, respectively, and the freedom of seizures at the same points were reached in 8 and 15.8%. The retention rates were 89.3% at the 3-month follow-up and 67.9% at the 6-month follow-up. The overall incidence of adverse events was 55.4%. The leading reported AEs were dizziness (39.3%) and somnolence (25%). Conclusions: Our study confirmed the efficacy and tolerability of adjunctive PER in Chinese patients in real-life conditions. Based on our treatment experience, a lower maintenance dose of PER would be needed in Chinese patients.