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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-4-24)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-4-24)
    Abstract: Apatinib and irinotecan are used as systematic therapies for advanced gastric adenocarcinoma (GAC) and gastroesophageal junction adenocarcinoma (GEJA), while the evidence for their combination as second-line therapy in these patients is limited. This study aimed to evaluate the efficacy and safety of second-line apatinib plus irinotecan for the treatment of GAC and GEJA. Methods In this prospective, multicenter phase II clinical study, 28 patients with advanced GAC or GEJA who received second-line apatinib plus irinotecan were recruited. Results In total, 1 (3.6%) patient achieved complete response, 7 (25.0%) patients achieved partial response, 13 (46.4%) patients had stable disease, and 4 (14.3%) patients showed progressive disease, while clinical response was not evaluable or not assessed in 3 (10.7%) patients. The objective response rate and disease control rate were 28.6% and 75.0%, respectively. Meanwhile, the median (95% confidence interval (CI)) progression-free survival (PFS) was 4.5 (3.9-5.1) months, and the median (95% CI) overall survival (OS) was 11.3 (7.4-15.1) months. By multivariate Cox regression analysis, male sex, liver metastasis, and peritoneal metastasis were independently associated with worse PFS or OS, while treatment duration ≥5 months was independently associated with better OS. In terms of the safety profile, 89.3% of patients experienced treatment-emergent adverse events of any grade, among which 82.1% of patients had grade 1-2 adverse events and 64.3% of patients had grade 3-4 adverse events. Conclusion Apatinib plus irinotecan as second-line therapy achieves a good treatment response and satisfactory survival with tolerable safety in patients with advanced GAC or GEJA.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 2
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 12 ( 2022-1-5)
    Abstract: Graves’ Ophthalmopathy (GO) is an organ-specific autoimmune disease that is often characterized by infiltration of orbital tissues and is considered as the most common extra-thyroid manifestation of Graves’ disease (GD). Although genetic susceptibility has been found to be critical for the phenotype of GO, the associated risk alleles in a single gene are generally insufficient to cause the disease. Accruing evidence has shown that epigenetic disorders can act as the potentially missing link between genetic risk and clinically significant disease development. Abnormal epigenetic modifications can lead to pro-inflammatory cascades and activation of orbital fibroblasts (OFs) by promoting the various inflammatory response pathways and regulating the diverse signaling molecules that are involved in the fibrogenesis and adipogenesis, thereby leading to the significant expansion of orbital tissues, fibrosis and inflammation infiltration. Additionally, emerging evidence has shown that the gut microbiome can possibly drive the pathogenesis of GO by influencing the secretion of Thyrotropin receptor antibody (TRAb) and T-helper 17 (Th17)/regulatory T cells (Treg) imbalance. This paper describes the latest epigenetic research evidence and progress made in comprehending the mechanisms of GO development, such as DNA methylation, histone modification, non-coding RNAs, and the gut microbiome.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2592084-4
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  • 3
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-11-24)
    Abstract: Lactic acid, a metabolic by-product of host and intestinal microbiota, has been recovered as an active signal molecule in the immune system. In this study, a lactic acid biosynthesis pathway that directly produces lactic acid from glucose rather than ethanol with high production was reconstructed in Saccharomyces cerevisiae . The engineered S. cerevisiae showed anti-inflammatory activity in dextran sulfate sodium (DSS)-induced mice with improved histological damage, increased mucosal barrier, and decreased intestinal immune response. Lactic acid regulated the macrophage polarization state and inhibited the expression of pro-inflammatory cytokines in vivo and in vitro . Increasing the macrophage monocarboxylic acid transporter-mediated active lactic acid uptake suppressed the excessive activation of the NLRP3 inflammasome and the downstream caspase-1 pathway in macrophages. Moreover, lactic acid promoted histone H3K9 acetylation and histone H3K18 lactylation. Meanwhile, the engineered S. cerevisiae altered the diversity and composition of the intestinal microbiota and changed the abundance of metabolic products in mice with colitis. In conclusion, this study shows that the application of engineered S. cerevisiae attenuated DSS-induced colitis in mice via suppressing macrophage pyroptosis and modulating the intestinal microbiota, which is an effective and safe treatment strategy for ulcerative colitis.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 4
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-8-20)
    Abstract: Patients with liver disease are susceptible to infection with Vibrio vulnificus ( V. vulnificus ), but the specific reasons remain elusive. Through RNA-seq, we found that when mice with alcoholic liver disease (ALD) were infected with V. vulnificus by gavage, compared with the Pair group, the small intestinal genes affecting intestinal permeability were upregulated; and the number of differentially expressed genes related to immune functions (e.g., such as cell chemotaxis, leukocyte differentiation, and neutrophil degranulation) decreased in the liver, spleen, and blood. Further analysis showed that the number of white blood cells decreased in the Pair group, whereas those in the ALD mice did not change significantly. Interestingly, the blood bacterial load in the ALD mice was about 100 times higher than that of the Pair group. After the ALD mice were infected with V. vulnificus , the concentrations of T cell proliferation-promoting cytokines (IL-2, IL-23) decreased. Therefore, unlike the Pair group, ALD mice had weaker immune responses, lower T cell proliferation-promoting cytokines, and higher bacterial loads post-infection, possibly increasing their susceptibility to V. vulnificus infection. These new findings we presented here may help to advance the current understanding of the reasons why patients with liver disease are susceptible to V. vulnificus infection and provides potential targets for further investigation in the context of treatment options for V. vulnificus sepsis in liver disease patient.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 5
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-12-13)
    Abstract: Brain metastasis (BM) is one of the most common failure patterns of pIIIA-N2 non-small cell lung cancer (NSCLC) after complete resection. Prophylactic cranial irradiation (PCI) can improve intracranial control but not overall survival. Thus, it is particularly important to identify the risk factors that are associated with BM and subsequently provide instructions for selecting patients who will optimally benefit from PCI. Methods and Materials Between 2011 and 2014, patients with pIIIA-N2 NSCLC who underwent complete resection in our institution were reviewed and enrolled in the study. Clinical characteristics, pathological parameters, treatment mode, BM time, and overall survival were analyzed. A nomogram was built based on the corresponding parameters by Fine and Gray’s competing risk analysis to predict the 1-, 3-, and 5-year probabilities of BM. Receiver operating characteristic curves and calibration curves were chosen for validation. A statistically significant difference was set as P & lt; 0.05. Results A total of 517 patients were enrolled in our retrospective study. The median follow-up time for surviving patients was 53.2 months (range, 0.50–123.17 months). The median age was 57 (range, 25–80) years. Of the 517 patients, 122 (23.6%) had squamous cell carcinoma, 391 (75.6%) received adjuvant chemotherapy, and 144 (27.3%) received post-operative radiotherapy. The 1-, 3-, and 5-year survival rates were 94.0, 72.9, and 66.0%, respectively. The 1-, 3-, and 5-year BM rates were 5.4, 15.7, and 22.2%, respectively. According to the univariate analysis, female, non-smokers, patients with non-squamous cell carcinoma, bronchial invasion, perineural invasion, and patients who received adjuvant chemotherapy were more likely to develop BM. In a multivariate analysis, non-squamous cell carcinoma (subdistribution hazard ratios, SHR: 3.968; 95% confidence interval, CI: 1.743–9.040; P = 0.0010), bronchial invasion (SHR: 2.039, 95% CI: 1.325–3.139; P = 0.0012), perineural invasion (SHR: 2.514, 95% CI: 1.058–5.976; P = 0.0370), and adjuvant chemotherapy (SHR: 2.821, 95% CI: 1.424–5.589; P = 0.0030) were independent risk factors for BM. A nomogram model was established based on the final multivariable analysis result. The area under the curve was 0.767 (95% CI, 0.758–0.777). Conclusions For patients with IIIA-N2 NSCLC after complete resection, a nomogram was established based on clinicopathological factors and treatment patterns for predicting the BM. Based on this nomogram, patients with a high risk of BM who may benefit from PCI can be screened.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Neuroscience Vol. 15 ( 2021-3-31)
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 15 ( 2021-3-31)
    Abstract: We aimed to determine the alterations in the subcortical structures of patients with idiopathic generalized epilepsy with tonic–clonic seizures (IGE-GTCS) via MRI volumetry and vertex-based shape analysis and to evaluate the relationships between MRI measures and drug responses. In a follow-up sample of 48 patients with IGE-GTCS and 48 matched normal controls (NCs), high-resolution 3D T 1 WI was performed at baseline. After 1 year of follow-up, 31 patients were classified as seizure free (SF) and 17 as drug resistant (DR). The volumes of subcortical structures were extracted, and vertex-based shape analysis was performed using FSL-Integrated Registration and Segmentation Toolbox (FSL-FIRST). Comparisons among groups were calculated adjusting for covariates [age, sex, and intracranial volume (ICV)]. Analysis of the relationships among imaging biomarkers along with frequency and duration was assessed using partial correlations. The differential imaging indicators were used as features in a linear support vector machine (LSVM). The DR group displayed significant regional atrophy in the volume of the left amygdala compared with NCs ( p = 0.004, false discovery rate corrected) and SF patients ( p = 0.029, uncorrected). Meanwhile, vertex-based shape analysis showed focal inward deformation in the basolateral subregion of the left amygdala in DR compared with the results for SF and NC ( p & lt; 0.05, FWE corrected). There were significant correlations between the volume changes and seizure frequency ( r = −0.324, p = 0.030) and between shape ( r = −0.438, p = 0.003) changes and seizure frequency. Moreover, the volume of the left thalamus in the DR group was significantly correlated with seizure frequency ( r = −0.689, p = 0.006). The SVM results revealed areas under the receiver operating characteristic curve of 0.82, 0.68, and 0.88 for the classification between SF and DR, between SF and NC, and between DR and NC, respectively. This study indicates the presence of focal atrophy in the basolateral region of the left amygdala in patients with IGE drug resistance; this finding may help predict drug responses and suggests a potential therapeutic target.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2411902-7
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 11 ( 2022-1-10)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2022-1-10)
    Abstract: BRCA1/2 mutation carriers are suggested with regular breast cancer surveillance screening strategies using mammography with supplementary MRI as an adjunct tool in Western countries. From a cost-effectiveness perspective, however, the benefits of screening modalities remain controversial among different mutated genes and screening schedules. Methods We searched the MEDLINE/PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases to collect and compare the results of different cost-effectiveness analyses. A simulated model was used to predict the impact of screening strategies in the target group on cost, life-year gained, quality-adjusted life years, and incremental cost-effectiveness ratio (ICER). Results Nine cost-effectiveness studies were included. Combined mammography and MRI strategy is cost-effective in BRCA1 mutation carriers for the middle-aged group (age 35 to 54). BRCA2 mutation carriers are less likely to benefit from adjunct MRI screening, which implies that mammography alone would be sufficient from a cost-effectiveness perspective, regardless of dense breast cancer. Conclusions Precision screening strategies among BRCA1/2 mutation carriers should be conducted according to the acceptable ICER, i.e., a combination of mammography and MRI for BRCA1 mutation carriers and mammography alone for BRCA2 mutation carriers. Systematic Review Registration PROSPERO, identifier CRD42020205471.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 8
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-5-13)
    Abstract: Waldenström macroglobulinemia/lymphoplasmacytoid lymphoma (WM/LPL) is a rare lymphoproliferative neoplasm characterized by clonally related lymphocytes, lymphoplasmacytic cells, and plasma cell proliferation. WM/LPL patients commonly present with elevated immunoglobulin, predominantly immunoglobulin M (IgM). Previous studies reported that thyroid dysfunction was associated with the development and progression of solid tumors. However, only limited information is available on the correlation between thyroid complications and lymphoid malignancies. The aim of our study was to explore the prognostic significance of thyroid complications in WM/LPL. Herein, 13.3% of WM/LPL patients were diagnosed with thyroid complications, which were significantly associated with unfavorable progression-free survival (PFS), overall survival (OS), and adverse treatment response. Co-existing thyroid disease was significantly related to alleviated serum IgM levels, providing an answer to practical problems. Furthermore, the presence of thyroid complications was identified as an independent prognostic indicator for PFS in WM/LPL. Incorporating the ISSWM score with thyroid complications was superior to ISSWM alone in risk stratification and prognostic prediction. Furthermore, subgroup analyses of WM/LPL patients revealed that subclinical hypothyroidism predicted undesirable outcomes at the early stage. These results were also supported by independent microarray dataset analyses. In conclusion, the primary strength of this study is that it provides robust real-world evidence on the prognostic role of thyroid complications, highlighting further clinical concerns in the management of WM/LPL patients.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 9
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 9 ( 2018-5-23)
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 10
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-10-26)
    Abstract: The aim of this study was to describe the treatment technique, outcomes, and complications of Schobinger stage IV head and neck arteriovenous malformations (HNAVMs) with associated high-output cardiac failure (HOCF) using ethanol and coils with the percutaneous suture technique. Methods From January 2015 to December 2019, 19 patients who had HNAVMs with associated HOCF were treated first with a percutaneous suture of the remarkably dilated dominant drainage vein (RDDOV) and subsequent embolization with coils and ethanol. The percutaneous suture of RDDOV was preferred to be performed, followed by the deployment of coils and the injection of absolute ethanol via transarterial approach, direct puncture approach, or both of them. Treatment outcomes and complication rates were evaluated at follow-up. Results A total of 19 patients who experienced HNAVMs with HOCF received 19 percutaneous suture procedures and 84 embolization procedures with ethanol and coils. Complete or & gt;90% shunt reduction of the AVM was achieved in 16 patients. Notably, 19 patients with New York Heart Association (NYHA) stage II improved to stage I, and the symptom of dyspnea disappeared after embolization. The symptoms of five patients with bleeding disappeared. All patients presented with cosmetic concerns; Four were cured, and eight had a clearly recognizable improvement. Of note, 19 (100%) patients presented with impairment of daily life, which was resolved. The minor complications were encountered and recovered by the self. No major complications occurred. Conclusion This study provides evidence that ethanol and coil embolotherapy is effective and safe in treating HOCF caused by HNAVMs with acceptable complications in these cases. The percutaneous suture technique for RDDOV management can act as an adjunct for embolotherapy.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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