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BackgroundFibrosarcoma is a rare sarcoma of the soft tissue in adults, occurring most commonly in the extremities. This study aimed to construct two web-based nomograms to predict overall survival (OS) and cancer-specific survival (CSS) in patients with extremity fibrosarcoma (EF) and validate it with multicenter data from the Asian/Chinese population.MethodPatients with EF in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were included in this study and were randomly divided into a training cohort and a verification cohort. The nomogram was developed based on the independent prognostic factors determined by univariate and multivariate Cox proportional hazard regression analyses. The predictive accuracy of the nomogram was validated with the Harrell’s concordance index (C-index), receiver operating curve, and calibration curve. Decision curve analysis (DCA) was utilized to compare the clinical usefulness between the novel model and the existing staging system.ResultA total of 931 patients finally were obtained in our study. Multivariate Cox analysis determined five independent prognostic factors for OS and CSS, namely, age, M stage, tumor size, grade, and surgery. The nomogram and the corresponding web-based calculator were developed to predict OS (https://orthosurgery.shinyapps.io/osnomogram/) and CSS (https://orthosurgery.shinyapps.io/cssnomogram/) probability at 24, 36, and 48 months. The C-index of the nomogram was 0.784 in the training cohort and 0.825 in the verification cohort for OS and 0.798 in the training cohort and 0.813 in the verification cohort for CSS, respectively, indicating excellent predictive performance. The calibration curves showed excellent agreement between the prediction by the nomogram and actual outcomes. Additionally, the results of DCA showed that the newly proposed nomogram was significantly better than the conventional staging system with more clinical net benefits. The Kaplan–Meier survival curves showed that patients assigned into the low-risk group had a more satisfactory survival outcome than the high-risk group.ConclusionIn this study, we constructed two nomograms and web-based survival calculators including five independent prognostic factors for the survival prediction of patients with EF, which could help clinicians make personalized clinical decisions.

PurposeTo investigate the impact of the pre-operative axial length (AL) on myopic shift (MS) 3 years after primary intraocular lens (IOL) implantation in congenital/developmental cataract patients.MethodsA retrospective study of patients who underwent congenital/developmental cataract surgery and primary IOL implantation at age 2–3 years at EENT Hospital was conducted. All patients were followed up regularly for at least 3 years after surgery. Refractive outcomes, including spherical equivalent (SE) and MS, were collected at each follow-up.ResultsForty eyes from 40 patients were included. The mean age at surgery was 2.56 ± 0.57 years old, and the mean follow-up time was 3.05 ± 0.22 years. Patients were divided into two groups: Group 1 included 20 patients with longer pre-operative ALs (≥22 mm), and Group 2 included 20 patients with average pre-operative ALs (

Age-related cataract (ARC) is one of the leading blinding eye diseases worldwide. Chronic oxidative stress and the apoptosis of human lens epithelial cells (HLECs) have been suggested to be the mechanism underlying cataract formation. Acetyl-11-keto-β-boswellic acid (AKBA) is a pentacyclic triterpene with antioxidative and antiapoptotic effects. In this study, we investigated the potential effects of AKBA on oxidative-induced HLECs injury and cataract formation. H2O2 was used to simulate HLECs oxidative injury in vitro, and Na2SeO3 was applied to establish an in vivo cataract model. In our current study, a cell counting kit-8 (CCK-8) assay was performed to evaluate the effects of H2O2 and AKBA on cell viability in vitro. Intracellular reactive oxygen species (ROS) levels were measured with the ROS assay to verify the antioxidant capacity of AKBA. Apoptotic cells were detected and measured by TUNEL staining and flow cytometry, and quantitative real-time (qRT)-PCR and Western blotting were applied to examine the transcription and expression of apoptosis-related proteins. Furthermore, immunofluorescence staining was performed to locate factor-erythroid 2-related factor 2 (Nrf2), and the protein levels of Nrf2, kelch-like ECH-associated protein 1 (Keap1) and heme oxygenase-1 (HO-1) were determined by Western blotting. Finally, we observed the degree of lens opacity and performed hematoxylin-eosin (H&E) staining to assess the protective effect of AKBA on cataract formation in vivo. AKBA increased HLECs viability under H2O2 stimulation, decreased intracellular ROS levels and alleviated the cell apoptosis rate in vitro. AKBA significantly decreased the expression of caspase-3 and Bax and increased the content of Bcl-2. The results of immunofluorescence and immunohistochemical staining proved that the expression and nuclear translocation of Nrf2 were activated with AKBA treatment in vivo and in vitro. Moreover, computational docking results showed that AKBA could bind specifically to the predicted Keap1/Nrf2 binding sites. After AKBA activation, Nrf2 dissociates from the Nrf2/Keap1 complex, translocates into the nucleus, and subsequently promotes HO-1 expression. In addition, AKBA attenuated lens opacity in selenite-induced cataracts. Overall, these findings indicated that AKBA alleviated oxidative injury and cataract formation by activating the Keap1/Nrf2/HO-1 cascade. Therefore, our current study highlights that AKBA may serve as a promising treatment for ARC progression.

ObjectiveIschemic infarction of pituitary apoplexy (PA) is a rare type of pituitary apoplexy. This study aims to characterize ischemic PA via clinical presentations, imaging data, histopathological manifestations, and focus on the management and prognosis of the disease.MethodsThis study retrospectively identified 46 patients with ischemic PA confirmed using histopathology at a single institution from January 2013 to December 2020. The clinical presentations, imaging data, laboratory examination, management, and outcomes were collected. We then summarized the clinical presentations, imaging features, intraoperative findings, and histopathological manifestations, and compared the outcomes based on the timing of surgical intervention.ResultsHeadache was the most common initial symptom (95.65%, 44/46), followed by visual disturbance (89.13%, 41/46), and nausea and vomiting (58.70%, 27/46). 91.3% of the patients had at least one pituitary dysfunction, with hypogonadism being the most common endocrine dysfunction (84.78%, 39/46). Cortisol dysfunction occurred in 24 (52.17%) patients and thyroid dysfunction occurred in 17 (36.96%). Typical rim enhancement and thickening of the sphenoid sinus on MRI were seen in 35 (85.37%) and 26 (56.52%) patients, respectively. Except for one patient with asymptomatic apoplexy, the remaining patients underwent early (≤ 1 week, 12 patients) and delayed (> 1 week, 33 patients) transsphenoidal surgery. Total tumor resection was achieved in 27 patients and subtotal tumor resection in 19 patients. At surgery, cottage cheese–like necrosis was observed in 50% (23/46) of the patients. At the last follow-up of 5.5 ± 2.7 years, 92.68% (38/41) of the patients had gained a significant improvement in visual disturbance regardless of surgical timing, and 65% of the patients were still receiving long-term hormone replacement therapy.ConclusionPatients with ischemic PA can be accurately diagnosed by typical imaging characteristics preoperatively. The timing of surgical intervention does not significantly affect the resolution of neurological and endocrinological dysfunctions. Preoperative endocrine dysfunctions are common and usually appear to be poor after surgical intervention.

Responses to neoadjuvant chemoradiotherapy (nCRT) and therapy-related toxicities in rectal cancer vary among patients. To provide the individualized therapeutic option for each patient, predictive markers of therapeutic responses and toxicities are in critical need. We aimed to identify the association of gut microbiome with and its potential predictive value for therapeutic responses and toxicities. In the present study, we collected fecal microbiome samples from patients with rectal cancer at treatment initiation and just after nCRT. Taxonomic profiling via 16S ribosomal RNA gene sequencing was performed on all samples. Patients were classified as responders versus non-responders. Patients were grouped into no or mild diarrhea and severe diarrhea. STAMP and high-dimensional class comparisons via linear discriminant analysis of effect size (LEfSe) were used to compare the compositional differences between groups. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was utilized to predict differences in metabolic function between groups. Ten patients were classified as responders and 12 patients were classified as non-responders. Fourteen patients experienced no or mild diarrhea and 8 patients experienced severe diarrhea. Several bacteria taxa with significantly different relative abundances before and after nCRT were identified. Similarly, several baseline bacteria taxa and predicted pathways with significantly different relative abundances between responders and non-responders or between patients no or mild diarrhea and severe diarrhea were identified. Specifically, Shuttleworthia was identified as enriched in responders and several bacteria taxa in the Clostridiales order etc. were identified as enriched in non-responders. Pathways including fatty acid metabolism were predicted to be enriched in responders. In addition, Bifidobacterium, Clostridia, and Bacteroides etc. were identified as enriched in patients with no or mild diarrhea. Pathways including primary bile acid biosynthesis were predicted to be enriched in patients with no or mild diarrhea. Together, the microbiota and pathway markers identified in this study may be utilized to predict the therapeutic responses and therapy-related toxicities of nCRT in patients with rectal cancer. More patient data is needed to verify the current findings and the results of metagenomic, metatranscriptomic, and metabolomic analyses will further mine key biomarkers at the compositional and functional level.

Age-related cataract (ARC) is one of the leading blinding eye diseases worldwide. Chronic oxidative stress and the apoptosis of human lens epithelial cells (HLECs) have been suggested to be themechanism underlying cataract formation. Acetyl-11-keto-ß-boswellic acid (AKBA) is a pentacyclic triterpene with antioxidative and antiapoptotic effects. In this study, we investigated the potential effects of AKBA on oxidative-induced HLECs injury and cataract formation. H2O2 was used to simulate HLECs oxidative injury in vitro, andNa2SeO3 was applied to establish an in vivo cataract model. In our current study, a cell counting kit-8 (CCK-8) assay was performed to evaluate the effects of H2O2 and AKBA on cell viability in vitro. Intracellular reactive oxygen species (ROS) levels were measured with the ROS assay to verify the antioxidant capacity of AKBA. Apoptotic cells were detected and measured by TUNEL staining and flow cytometry, and quantitative real-time (qRT)-PCR and Western blotting were applied to examine the transcription and expression of apoptosis-related proteins. Furthermore, immunofluorescence staining was performed to locate factor-erythroid 2-related factor 2 (Nrf2), and the protein levels of Nrf2, kelch-like ECH-associated protein 1 (Keap1) and heme oxygenase-1 (HO-1) were determined by Western blotting. Finally, we observed the degree of lens opacity and performed hematoxylin-eosin (H&E) staining to assess the protective effect of AKBA on cataract formation in vivo. AKBA increased HLECs viability under H2O2 stimulation, decreased intracellular ROS levels and alleviated the cell apoptosis rate in vitro. AKBA significantly decreased the expression of caspase-3 and Bax and increased the content of Bcl-2. The results of immunofluorescence and immunohistochemical staining proved that the expression and nuclear translocation of Nrf2 were activated with AKBA treatment in vivo and in vitro. Moreover, computational docking results showed that AKBA could bind specifically to the predicted Keap1/Nrf2 binding sites. After AKBA activation, Nrf2 dissociates from the Nrf2/Keap1 complex, translocates into the nucleus, and subsequently promotes HO-1 expression. In addition, AKBA attenuated lens opacity in selenite-induced cataracts. Overall, these findings indicated that AKBA alleviated oxidative injury and cataract formation by activating the Keap1/Nrf2/HO-1 cascade. Therefore, our current study highlights that AKBA may serve as a promising treatment for ARC progression. [ABSTRACT FROM AUTHOR]