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1.
J Card Fail ; 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34624511

RESUMO

OBJECTIVES: To determine national trends and long term outcomes of post myocardial infarction (MI) heart failure. BACKGROUND: Myocardial infarction (MI) can be complicated by heart failure; there are limited data describing the contemporary patterns and clinical implications of post-MI heart failure. METHODS: We studied MI patients aged ≥ 65 years from 2000-2013 in a Medicare database. New onset heart failure post-MI was defined as either heart failure during index MI admission or a hospitalization for heart failure within 1 year of index MI event. A trend analysis of the incidence of heart failure was performed, differences were examined by Gray tests. The 5-year mortality rates were evaluated and differences among heart failure cohorts were ascertained by Gray tests. RESULTS: There were a total of 1,531,638 MI patients and 565,291 patients had heart failure (36.0%). The rate of heart failure during index admission was 32.3% and the frequency of heart failure hospitalization within 1 year was 10.4%. Patients with heart failure were older (81 vs 77 years). The temporal trend from 2001-2012 suggested a reduction in the incidence of heart failure during index admission (2001: 34.7%, 2012: 31.2%, p-trend < 0.01), as well as heart failure hospitalization within 1 year (2001: 11.3%, 2012: 8.7%, p-trend < 0.01). The 5-year mortality rate among patients without heart failure was 38.4% and for patients with any heart failure it was 68.7%. CONCLUSION: Post-MI heart failure in older adults occurs in 1 in 3 patients within 1 year; heart failure portends significantly higher long-term mortality.

2.
Biomed Pharmacother ; 144: 112253, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34607106

RESUMO

Iron supplementation is necessary for the treatment of anemia, one of the most frequent complications in inflammatory bowel disease (IBD). However, oral iron supplementation leads to an exacerbation of intestinal inflammation. Gut barrier plays a key role in the pathogenesis of IBD. The aim of this study was to characterize the interrelationship between systemic iron, intestinal barrier and the development of intestinal inflammation in a dextran sulfate sodium (DSS) induced experimental colitis mice model. We found that DSS-treated mice developed severe inflammation of colon, but became much healthy when intraperitoneal injection with iron. Iron supplementation alleviated colonic and systemic inflammation by lower histological scores, restorative morphology of colonic villi, and reduced expression of pro-inflammatory cytokines. Moreover, intraperitoneal supplementation of iron enhanced intestinal barrier function by upregulating the colonic expressions of tight junction proteins, restoring intestinal immune homeostasis by regulating immune cell infiltration and T lymphocyte subsets, and increasing mucous secretion of goblet cells in the colon. High-throughput sequencing of fecal 16 S rRNA showed that iron injection significantly increased the relative abundance of Bacteroidetes, which was suppressed in the gut microbiota of DSS-induced colitis mice. These results provided evidences supporting the protective effects of systemic iron repletion by intraperitoneal injection of iron on intestinal barrier functions. The finding highlights a novel approach for the treatment of IBD with iron injection therapy.

3.
J Exp Clin Cancer Res ; 40(1): 304, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34583750

RESUMO

BACKGROUND: Tumor-associated macrophages (TAMs) are key regulators of the complex interplay between cancer and the immune microenvironment. Tumor cell-derived spondin 2 (SPON2) is an extracellular matrix glycoprotein that has complicated roles in recruitment of macrophages and neutrophils during inflammation. Overexpression of SPON2 has been shown to promote tumor cell migration in colorectal cancer (CRC). However, the mechanism by which SPON2 regulates the accumulation of TAMs in the tumor microenvironment (TME) of CRC is unknown. METHODS: Immunohistochemistry was used to examine SPON2 expression in clinical CRC tissues. In vitro migration assays, transendothelial migration assays (iTEM), and cell adhesion assays were used to investigate the effects of SPON2 on monocyte/macrophage migration. Subcutaneous tumor formation and orthotopic implantation assays were performed in C57 BL/6 mice to confirm the effects of SPON2 on TAM infiltration in tumors. RESULTS: SPON2 expression is positively correlated with M2-TAM infiltration in clinical CRC tumors and poor prognosis of CRC patients. In addition, SPON2 promotes cytoskeletal remodeling and transendothelial migration of monocytes by activating integrin ß1/PYK2 axis. SPON2 may indirectly induce M2-polarization through upregulating cytokines including IL10, CCL2 and CSF1 expression in tumor cells. Blocking M2 polarization and Macrophage depletion inhibited the SPON2-induced tumors growth and invasion. Furthermore, blocking the SPON2/integrin ß1/PYK2 axis impairs the transendothelial migration of monocytes and cancer-promoting functions of TAMs in vivo. CONCLUSIONS: Our findings demonstrate that SPON2-driven M2-TAM infiltration plays an important role during CRC tumor growth and metastasis. SPON2 may be a valuable biomarker guiding the use of macrophage-targeting strategies and a potential therapeutic target in advanced CRC.

4.
ACS Nano ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34586802

RESUMO

The clinical application of small interfering RNA (siRNA) drugs provides promising opportunities to develop treatment strategies for autoimmune inflammatory diseases. In this study, siRNAs targeting the endoplasmic reticulum to nucleus signaling 1 (ERN1) gene (siERN1) were screened. Two cationic polymers, polyethylenimine (PEI) and poly(ß-amino amine) (PBAA), which can improve the efficiency of the siRNA transfection, were used as siERN1 delivery carriers. They were implemented to construct a nanodrug delivery system with macrophage-targeting ability and dual responsiveness for the treatment of autoimmune inflammatory diseases. In terms of the mechanism, siERN1 can regulate the intracellular calcium ion concentration by interfering with the function of inositol 1,4,5-trisphosphate receptor 1/3 (IP3R1/3) and thus inducing M2 polarization of macrophages. Furthermore, siERN1-nanoprodrug [FA (folic acid)-PEG-R(RKKRRQRRR)-NPs(ss-PBAA-PEI)@siERN1] acts as a conductor of macrophage polarization by controlling the calcium ion concentration and is an inhibitor of MyD88-dependent Toll-like receptor signaling. The results revealed that the FA-PEG-R-NPs@siERN1 has universal biocompatibility, long-term drug release responsiveness, superior targeting properties, and therapeutic effects in mouse collagen-induced arthritis and inflammatory bowel disease models. In conclusion, this study reveals a potential strategy to treat autoimmune inflammatory disorders.

5.
J Agric Food Chem ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519206

RESUMO

Proteins, vitamins, and phenols are often present together in foods, but they are sensitive to environmental factors. Folic acid (FA), a synthetic form of folate, decomposes under light, leading to protein oxidation. Caffeic acid (CA), a phenolic acid, exhibits remarkable activity for scavenging reactive molecules. The exploitation of their interactions offers opportunities for designing the stabilizing system. In this study, FA-photodecomposition-induced protein (ß-lactoglobulin, α-lactalbumin, bovine serum albumin, and ß-casein) damage and its inhibition by CA were investigated in terms of protein composition and structural change. The results indicated that FA photoproducts oxidized the proteins via the electron transfer pathway, leading to degradation, aggregation, and unfolding. At the same time, photostability of FA, CA, and proteins in the tertiary mixture was better than that of any individual components. The antioxidant activity of the proteins contributed to their protection for FA. CA and its products inhibited FA photodecomposition and the photodecomposition-induced protein oxidation by trapping excited states.

6.
Medicine (Baltimore) ; 100(35): e26996, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477129

RESUMO

ABSTRACT: To reveal the role of the postoperative choledochoscopy in treating the residual calculi in the caudate lobe (CL) of the liver.We recruited 66 patients with T-tube/percutaneous transhepatic cholangioscopy tract who still had residual gallstones in the CL at least 6 weeks after the operation. Imaging examinations determined the gallstones' locations in the patients, and all of them underwent the postoperative choledochoscopic examination through the T-tube/percutaneous transhepatic cholangioscopy tract for therapeutic intervention.Among the 66 patients, the residual gallstones were mostly located in the Spiegel lobe (48/66, 72.7%), and the residual gallstones that located in the origin of the CL bile branches were successfully determined in the 57 patients (57/66, 86.4%), the remaining 9 patients were unclear because the proximal ducts were severely narrow or even atresia. The mean frequency of the postoperative choledochoscopy was 3.6 (range, 1-10) times. There were 9 patients with complications, and no mortality occurred. In the origin-proved 57 patients, 6 patients failed to remove the gallstones altogether, and the final residual gallstone clearance rate was 77.3% (51/66). There was no significant difference between the Spiegel lobe and the other parts of the CL in determining the bile duct's origins, gallstone clearance rate, and complications. However, the frequency of choledochoscopy in the other parts of the CL was more than in the Spiegel lobe.The postoperative choledochoscopy, an essential method for treating the residual gallstones in the CL, commands high efficiency for calculi extraction and fewer complications. The main reasons for failing to remove the residual gallstones are that the bile duct's origins could not be determined, and the distal bile ducts are atretic in the CL.


Assuntos
Sistema Biliar/diagnóstico por imagem , Coledocolitíase/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Sistema Biliar/anormalidades , Feminino , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos
8.
J Transl Med ; 19(1): 379, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488791

RESUMO

BACKGROUND: Since interferon regulatory factor (IRF) family functions in immune response to viral infection, its role in colorectal cancer (CRC) has not been inspected before. This study tries to investigate members of IRF family using bioinformatics approaches in aspect of differential expressions, biological function, tumor immune infiltration and clinical prognostic value for patients with CRC. METHODS: Transcriptome profiles data, somatic mutations and clinical information of CRC were obtained from COAD/READ dataset of The Cancer Genome Atlas (TCGA) as a training set. Gene expression data (GSE17536 and GSE39582) were downloaded from the Gene Expression Omnibus as a validating set. A random forest algorithm was used to score the risk for every case. Analyzing gene and function enrichment, constructing protein-protein interaction and noncoding RNA network, identifying hub-gene, characterizing tumor immune infiltration, evaluating differences in tumor mutational burden (TMB) and sensitivity to chemotherapeutics or immunotherapy were performed by a series of online tools and R packages. Immunohistochemical (IHC) examinations were carried out validation in tissue samples. RESULTS: Principal-component analysis (PCA) suggested that the transcript expression levels of nine members of IRF family differed between normal colorectum and CRC. The risk score constructed by IRF family not only acted as an independent factor for predicting survival in CRC patients with different biological processes, signaling pathways and TMB, but also indicated different immunotherapy response with diverse immune and stromal cells infiltration. IRF3 and IRF7 were upregulated in CRC and suggested a shorter survival time in patients with CRC. Differentially expressed members of IRF family exhibited varying degrees of immune cell infiltration. IHC analysis showed a positive association between IRF3 and IRF7 expression and tumor-infiltrating immune cells, including CD4+ T cell and CD68+ macrophages. CONCLUSIONS: On account of differential expression, IRF family members can help to predict both response to immunotherapy and clinical prognosis of patients with CRC. Our bioinformatic investigation not only gives a preliminary picture of the genetic features as well as tumor microenvironment, but it may provide a clue for further experimental exploration and verification on IRF family members in CRC.


Assuntos
Neoplasias Colorretais , Fatores Reguladores de Interferon , Biomarcadores Tumorais , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores Reguladores de Interferon/genética , Prognóstico , Microambiente Tumoral
9.
J Glob Health ; 11: 05021, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552726

RESUMO

Background: Evidence has revealed that nonpharmaceutical interventions (NPIs) were effective in attenuating the spread of COVID-19. However, policymakers have encountered difficulty in identifying the most effective policies under different circumstances. This study investigated the relative effectiveness of different NPIs and vaccination in prolonging COVID-19 case doubling time (DT). Methods: The study sample consisted of observations from 137 countries during 1 January 2020 to 13 June 2021. DT was calculated on a daily basis per country. Data were retrieved from the Oxford COVID-19 Government Response Tracker, World Development Indicators, and Worldwide Governance Indicators. To capture policy intervention dynamics, we combined a random-effect growth-curve model with nonstandard interrupted time series analysis. We also evaluated the association of policy measures with DT for different outbreak stages and levels of government effectiveness. Results: Vaccine rollouts, workplace closures, and school closures were relatively effective. For each day that these measures were implemented, the DT increased by 1.96% (95% confidence interval (CI) = 0.63 to 3.29; P = 0.004), 1.41% (95% CI = 0.88 to 1.95%; P < 0.001) and 1.38% (95% CI = 0.95 to 1.81%; P < 0.001), respectively. Workplace and school closures were positively associated with DT at all stages; however, the associations weakened in later stages, where vaccine rollouts appeared to be most effective in prolonging DT (95% CI = 1.51% to 3.04%; P < 0.05). For countries with a high level of government effectiveness, most of the containment measures evaluated were effective; vaccine rollouts had the greatest effect size. For countries with medium or low levels of government effectiveness, only the closure of workplaces was consistently associated with prolonged DT. Conclusions: The effectiveness of vaccine rollouts outweighed that of NPIs, especially in the later outbreak stages. However, vaccination was not associated with prolonged case DT in countries with lower levels of government effectiveness, probably due to low vaccine coverage. Among the NPIs examined, workplace closures were highly effective across all outbreak stages and levels of government effectiveness. Our findings suggest that mass vaccination is critical to reducing SARS-CoV-2 transmission, especially in countries where NPIs are less effective.


Assuntos
COVID-19 , Governo , Humanos , SARS-CoV-2 , Instituições Acadêmicas , Vacinação
10.
Hepatology ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34580888

RESUMO

Poor response to ionizing radiation (IR) due to resistance remains a clinical challenge. Altered metabolism represents a defining characteristic of nearly all types of cancers. However, how radio-resistance is linked to metabolic reprogramming remains elusive. The present study establishes a metabolic phenotype that mediates radiation resistance in hepatocellular carcinoma (HCC), whereby increased glucose flux leads to glucose addiction in radio-resistant HCC cells and a corresponding increase in glycerophospholipids biosynthesis to enhance the levels of cardiolipin. Accumulation of cardiolipin dampens the effectiveness of IR by inhibiting cytochrome c release to initiate apoptosis. We also demonstrate that mTORC1 signaling-mediated translational control of hypoxia inducible factor-1α (HIF-1α) and sterol regulatory element-binding protein-1 (SREBP1) remodels such metabolic cascade. Targeting mTORC1 or glucose to cardiolipin synthesis, in combination with IR, strongly diminishes tumor burden. Finally, activation of glucose metabolism predicts poor response to radiotherapy in cancer patients. Taken together, we uncover here a previously unrecognized link between radiation resistance and metabolic integration and suggest that metabolically dismantling the radio-resistant features of tumors may provide potential combination approaches for radiotherapy in HCC.

11.
Lab Chip ; 21(20): 4005-4015, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34476431

RESUMO

Rapid and personalized single-cell drug screening testing plays an essential role in acute myeloid leukemia drug combination chemotherapy. Conventional chemotherapeutic drug screening is a time-consuming process because of the natural resistance of cell membranes to drugs, and there are still great challenges related to using technologies that change membrane permeability such as sonoporation in high-throughput and precise single-cell drug screening with minimal damage. In this study, we proposed an acoustic streaming-based non-invasive single-cell drug screening acceleration method, using high-frequency acoustic waves (>10 MHz) in a concentration gradient microfluidic device. High-frequency acoustics leads to increased difficulties in inducing cavitation and generates acoustic streaming around each single cell. Therefore, single-cell membrane permeability is non-invasively increased by the acoustic pressure and acoustic streaming-induced shear force, which significantly improves the drug uptake process. In the experiment, single human myeloid leukemia mononuclear (THP-1) cells were trapped by triangle cell traps in concentration gradient chips with different cytarabine (Ara-C) drug concentrations. Due to this dual acoustic effect, the drugs affect cell viability in less than 30 min, which is faster than traditional methods (usually more than 24 h). This dual acoustic effect-based drug delivery strategy has the potential to save time and reduce the cost of drug screening, when combined with microfluidic technology for multi-concentration drug screening. This strategy offers enormous potential for use in multiple drug screening or efficient drug combination screening in individualized/personalized treatments, which can greatly improve efficiency and reduce costs.

13.
Food Chem ; 371: 131122, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34571406

RESUMO

Tea seed oil is rich in phenols with good antioxidant capacity. However, the antioxidant capacity evaluation of tea seed oil polyphenols is not deep enough, which mainly focusing on the evaluation of the chemical system. Thirty-nine phenols were tentatively identified by UPLC-ESI-MS/MS analysis, including flavonoids and phenolic acids. The antioxidant capacity of phenol extracts was investigated in vitro and in vivo. The chemical assays showed the extracts had good proton and electron transfer capabilities. The CAA assay indicated the IC50 of the extracts was 77.93 ± 4.80 µg/mL and cell antioxidant capacity of the extracts was 101.05 ± 6.70 µmol·QE/100 g of oil. The animal experiments suggested phenol extracts could significantly improve the organ index, reduce malondialdehyde content, and increase superoxide dismutase, glutathione peroxidase and total antioxidant capacity (p < 0.05). This study was contributed to the antioxidant capacity of phenol extracts of tea seed oil by comprehensive evaluation.

14.
Opt Lett ; 46(17): 4264-4267, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469990

RESUMO

A broad linewidth and a lack of spectral analysis limit the applications of plasmonic sensors. In this Letter, a plasmonic sensor with a large sensitivity in the terahertz (THz) range is proposed based on high-quality factor (>1000) surface lattice resonance in subwavelength near-flat metallic gratings. Moreover, such a highly selective spectral manipulating scheme, plus the greatly localized plasmonic resonance, enables miniaturized spectroscopy based on a single detector by integrating an electro-optical material with the gratings. A spectral resolution of 0.1 GHz at a center frequency of 1.1 THz is predicted showing a four times improvement of measuring efficiency. This technique shows promising potential in on-site matter inspection and point-of-care testing.

15.
Clin Psychol Rev ; 89: 102069, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34454322

RESUMO

The present meta-analytic review examined the associations between different forms of trauma and mental disorders among prisoners and ex-prisoners. Studies published from 1998 to March 31 2021 were identified by searching PsycINFO, PubMed, Medline and Web of Science. Data were meta-analyzed using a random-effect model. Moderator and mediator analyses were conducted. The protocol was registered in PROSPERO (CRD42020181587). We identified 62 studies (50 non-duplicated samples) with 15,115 (97.86%) prisoners and 330 (2.14%) ex-prisoners in 16 countries. A multi-level meta-analysis found that overall trauma was positively associated with more diagnoses or symptoms of mental disorders (Zr = 0.198, 95% CI = [0.167, 0.229], p < 0.001). Stronger effect sizes were found between childhood trauma (Zr = 0.357, 95% CI = [0.147, 0.568], p < 0.01) and sexual trauma (Zr = 0.326, 95% CI = [0.216, 0.435], p < 0.001) and stress-related disorders. Multilevel moderator analysis showed that effect size was stronger in imprisonment trauma (ß = 0.247, 95% CI = [0.177, 0.316], p < 0.01), mixed trauma (ß = 0.234, 95% CI = [0.196, 0.272], p < 0.001), and stress-related disorders (ß = 0.261, 95% CI = [0.214, 0.307], p < 0.01). Associations between trauma and mental disorders were mediated by social support but not coping. Our findings provide an evidence base for future research on the impact of trauma and inform assessments and interventions in correctional settings.

16.
J Environ Manage ; 298: 113529, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34426226

RESUMO

The northern part of the Yangtze River Delta (YRD) region in China suffers from high concentrations of fine particular matter (PM2.5) during the past years yet received much less attention compared to the other parts of the YRD region. In this study, we integrated observational data, control policies and strategies, and air quality simulations to develop PM2.5 attainment demonstration by year 2030 for the city of Bengbu, which represents a typical non-compliant city in the northern YRD region. In 2018, the annual average PM2.5 concentration in Bengbu was 51.8 µg/m3, which was 48 % higher than the standard of 35 µg/m3 set by the National Ambient Air Quality Standards (NAAQS). Different future emission scenarios were developed for year 2025 as mid-term and year 2030 as long-term. Integrated meteorology and air quality modeling system together with monitoring data was applied to predict the air quality under the future emission scenarios. Results show that when a conservative emission reduction ratio of 40 % was assumed for surrounding regions, the annual average PM2.5 concentration in Bengbu could meet the target value by 2030, in which case emissions of SO2, NOx, PM2.5, VOCs, and NH3 need to be reduced by 70.6 %, 43.5 %, 47.2 %, 33.4 %, and 47.5 %, respectively. PM2.5 concentration in Bengbu is not only controlled by local emission reductions but also affected by emission reductions of surrounding regions as well as contribution from long-range transport. More attentions need to be paid to the control of VOCs emissions in the near future to avoid increase of ozone concentrations while reducing PM2.5. Our results provide scientific support for the local government to formulate future air pollution prevention and control strategies, sub-regional joint-control among surrounding cities, as well as trans-regional joint-control between the north China and the YRD region.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Cidades , Monitoramento Ambiental , Material Particulado/análise
17.
J Am Heart Assoc ; 10(16): e020528, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34387132

RESUMO

Background Evidence suggests intracerebral hemorrhage survivors have earlier recovery compared with ischemic stroke survivors. The Centers for Medicare and Medicaid Services prospective payment system instituted documentation rules for inpatient rehabilitation facilities (IRFs) in 2010, with the goal of optimizing patient selection. We investigated whether these requirements limited IRF and increased skilled nursing facility (SNF) use compared with home discharge. Methods and Results Intracerebral hemorrhage discharges to IRF, SNF, or home were estimated using GWTG (Get With The Guidelines) Stroke registry data between January 1, 2008, and December 31, 2015 (n=265 444). Binary hierarchical models determined associations between the 2010 Rule and discharge setting; subgroup analyses evaluated age, geographic region, and hospital type. From January 1, 2008, to December 31, 2009, 45.5% of patients with intracerebral hemorrhage had home discharge, 22.2% went to SNF, and 32.3% went to IRF. After January 1, 2010, there was a 1.06% absolute increase in home discharge, a 0.46% increase in SNF, and a 1.52% decline in IRF. The adjusted odds of IRF versus home discharge decreased 3% after 2010 (adjusted odds ratio [aOR], 0.97; 95% CI, 0.95-1.00). Lower odds of IRF versus home discharge were observed in people aged <65 years (aOR, 0.92; 95% CI, 0.89-0.96), Western states (aOR, 0.89; 95% CI, 0.84-0.95), and nonteaching hospitals (aOR, 0.90; 95% CI, 0.86-0.95). Adjusted odds of SNF versus home discharge increased 14% after 2010 (aOR, 1.14; 95% CI, 1.11-1.18); there were significant associations in all age groups, the Northeast, the South, the Midwest, and teaching hospitals. Conclusions The Centers for Medicare and Medicaid Services 2010 IRF prospective payment system Rule resulted in fewer discharges to IRF and more discharges to SNF in patients with intracerebral hemorrhage. Health policy changes potentially affect access to intensive postacute rehabilitation.

18.
Asian J Surg ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34384677

RESUMO

AIM: There lacks a predictive model for overall survival (OS) of node-negative perihilar cholangiocarcinoma (PHC). This study aimed at developing and validating a prognostic nomogram to predict OS of node-negative PHC after resection. METHODS: We established a nomogram via multivariate regression analysis by using the design cohort (n = 410, obtained from Surveillance, Epidemiology, and End Results database), and its external verification was done in the validation cohort (n = 100, the First Affiliated Hospital of Sun Yat-sen University). Predictive accuracy of the nomogram was assessed by concordance-index (C-index), calibration curves, and decision curve analysis (DCA). Performance of the nomogram was compared with the American Joint Committee on Cancer (AJCC) staging system. RESULTS: Multivariate regression analysis revealed that age, tumor grade, and the count of examined lymph nodes were independent prognostic factors for OS of node-negative PHC. The nomogram had a C-index of 0.603 and 0.626 in design cohort and validation cohort, respectively, which was better than that of AJCC staging system (both p < 0.05). The calibration curves showed good consistency between actual and nomogram-predicted OS probabilities. DCA showed that nomogram had better clinical usefulness. Furthermore, the nomogram-predicted scores could stratify the patients into three risk groups, and patients in higher risk group had worse prognosis than those in lower risk group (all p < 0.05). CONCLUSION: The proposed nomogram had a better prognostic accuracy than the AJCC staging system in predicting postoperative OS of node-negative PHC. It was helpful to guide the adjuvant therapeutic strategies for node-negative PHC.

19.
BMC Cancer ; 21(1): 915, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384377

RESUMO

BACKGROUND: Intracranial hemangiopericytoma is a rare disease and surgery is the mainstay treatment. Although postoperative adjuvant radiotherapy is often used, there are no reports comparing different radiotherapy techniques. The purpose of this study is to analyze the impact of post-operative radiotherapy and different radiotherapy technique on the results in patients with intracranial hemangiopericytoma (HPC). METHODS: We retrospectively reviewed 66 intracranial HPC patients treated between 1999 and 2019 including 29 with surgery followed by radiotherapy (11 with intensity-modulated radiotherapy (IMRT) and 18 with stereotactic radiosurgery (SRS)) and 37 with surgery alone. Chi-square test was used to compare the clinical characteristic between the groups. The Kaplan-Meier method was used to analyze overall survival (OS) and recurrence-free survival (RFS). Multivariate Cox proportional hazards models were used to examine prognostic factors of survival. We also underwent a matched-pair analysis by using the propensity score method. RESULTS: The crude local control rates were 58.6% in the surgery plus post-operative radiotherapy group (PORT) and 67.6% in the surgery alone group (p = 0.453). In the subgroup analysis of the PORT patients, local controls were 72.7% in the IMRT group and 50% in the SRS group (p = 0.228). The median OS in the PORT and surgery groups were 122 months and 98 months, respectively (p = 0.169). The median RFS was 96 months in the PORT group and 72 months in the surgery alone group (p = 0.714). Regarding radiotherapy technique, the median OS and RFS of the SRS group were not significantly different from those in the IMRT group (p = 0.256, 0.960). The median RFS were 112 and 72 months for pathology grade II and III patients, respectively (p = 0.001). Propensity score matching did not change the observed results. CONCLUSION: In this retrospective analysis, PORT did not improve the local control rates nor the survivals. The local control rates after IMRT and SRS were similar even though the IMRT technique had a much higher biological dose compared with the SRS technique.

20.
Neurobiol Dis ; 158: 105470, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34371143

RESUMO

Mitochondrial superoxide (O2-) production is implicated in aging, neurodegenerative disease, and most recently epilepsy. Yet the specific contribution of neuronal O2- to these phenomena is unclear. Here, we selectively deleted superoxide dismutase-2 (SOD2) in neuronal basic helix-loop-helix transcription factor (NEX)-expressing cells restricting deletion to a subset of excitatory principle neurons primarily in the forebrain (cortex and hippocampus). This resulted in nSOD2 KO mice that lived into adulthood (2-3 months) with epilepsy, selective loss of neurons, metabolic rewiring and a marked mitohormetic gene response. Surprisingly, expression of an astrocytic gene, glial fibrillary acidic protein (GFAP) was significantly increased relative to WT. Further studies in rat primary neuron-glial cultures showed that increased mitochondrial O2-, specifically in neurons, was sufficient to upregulate GFAP. These results suggest that neuron-specific mitochondrial O2- is sufficient to drive a complex and catastrophic epileptic phenotype and highlights the ability of SOD2 to act in a cell-nonautonomous manner to influence an astrocytic response.

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