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1.
Int J Oncol ; 59(5)2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34664682

RESUMO

The Nectin cell adhesion molecule (Nectin) family members are Ca2+­independent immunoglobulin­like cellular adhesion molecules (including Nectins 1­4), involved in cell adhesion via homophilic/heterophilic interplay. In addition, the Nectin family plays a significant role in enhancing cellular viability and movement ability. In contrast to enrichment of Nectins 1­3 in normal tissues, Nectin­4 is particularly overexpressed in a number of tumor types, including breast, lung, urothelial, colorectal, pancreatic and ovarian cancer. Moreover, the upregulation of Nectin­4 is an independent biomarker for overall survival in numerous cancer types. A large number of studies have revealed that high expression of Nectin­4 is closely related to tumor occurrence and development in various cancer types, but the manner in which Nectin­4 protein contributes to the onset and development of these malignancies is yet unknown. The present review summarizes the molecular mechanisms and functions of Nectin­4 protein in the biological processes and current advances with regard to its expression and regulation in various cancer types.

2.
BMC Genomics ; 22(1): 653, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34511071

RESUMO

BACKGROUND: As non-coding RNA molecules of more than 200 bp in length, long non-coding RNAs (lncRNAs) play a variety of roles in biological processes, including regulating the immune responses to bacterial infections. In recent years, there have been many in-depth studies on mammalian lncRNAs, but the relevant studies in fish are very limited. Meanwhile, since lncRNAs are not conserved among species, it is difficult to apply the existing results directly to unstudied species. RESULTS: To obtain the information of lncRNAs in Megalobrama amblycephala, one of the most economically important freshwater fish in China, also to better understand the biological significance of lncRNAs in the immunity system, the fish liver at 0, 4, 12, 24, and 72 h post Aeromonas hydrophila infection (hpi) were obtained for lncRNA-sequencing (lncRNA-seq). A total of 14,849 lncRNAs were identified, and 2196 lncRNAs showed significant differences at different time points post A. hydrophila infection. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the target genes of the differentially expressed lncRNAs were enriched in several pathways related to immune such as apoptosis, inflammation, and immune response. Time-specific modules were then identified, using weighted correlation network analysis (WGCNA), and 28 modules significantly correlated with different time point after infection were found. Furthermore, four immune-related genes and six lncRNAs in the time-specific modules were subsequently verified by RT-qPCR. CONCLUSIONS: The above findings reveal the discovery of widespread differentially expressed lncRNAs in the M. amblycephala liver post A. hydrophila infection, suggesting that lncRNAs might participate in the regulation of host response to bacterial infection, enriching the information of lncRNAs in teleost and providing a resources basis for further studies on the immune function of lncRNAs.


Assuntos
Cyprinidae , RNA Longo não Codificante , Aeromonas hydrophila , Animais , Cyprinidae/genética , Fígado , RNA Longo não Codificante/genética , RNA Mensageiro/genética
3.
Cancer Manag Res ; 13: 6101-6111, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34377028

RESUMO

Introduction: Cranial radiotherapy (CRT) is the main treatment for non-small cell lung cancer (NSCLC) with brain metastasis (BM) and non-EGFR/ALK/ROS1-TKIs indication, and anlotinib can improve overall prognosis. However, the clinical effects of CRT combined with anlotinib for the treatment of NSCLC with BM remain unclear. Methods: We retrospectively analyzed the clinical effects of anlotinib + CRT versus CRT alone in NSCLC patients with BM and non-EGFR/ALK/ROS1-TKIs indication from September 2016 to June 2020. The progression-free survival (PFS) and overall survival (OS) of anlotinib + CRT versus CRT alone were analyzed. After evaluation of the clinical characteristics to generate a baseline, the independent prognostic factors for intracranial PFS (iPFS) and OS were subjected to univariate and multivariate analysis. Finally, subgroup analysis for iPFS and OS was performed to assess treatment effects using randomized stratification factors and stratified Cox proportional hazards models. Results: This study included data for 73 patients with BM at baseline. Of the 73 patients, 45 patients received CRT alone, and 28 patients received CRT + anlotinib. There was no significant difference in clinical features between the two groups (P > 0.05). Compared with the CRT group, the combined group had longer iPFS (median iPFS [miPFS]: 3.0 months vs 11.0 months, P = 0.048). However, there were no significant differences in OS, extracranial PFS, and systemic PFS. For clinical features, univariate and multivariate analysis showed that the plus anlotinib treatment was an independent advantage predictor of iPFS (hazard ratio [HR] 0.51; 95% confidence interval [CI] 0.27-0.95; P = 0.04), and age ≥57 years (HR 1.04, 95% CI 1.01-1.08, P = 0.014) and KPS score ≤80 (HR 1.04, 95% CI 1.01-1.08, P = 0.014) were independent disadvantage predictors of OS (P < 0.05). In addition, although this difference was not statistically significant (p > 0.05), the patients with the anlotinib + local CRT (LCRT) treatment had the longest iPFS (miPFS: 27.0 months) and OS (median OS [mOS]: 36 months). The miPFS and mOS values for the LCRT group were 11 months and 18 months, respectively, with shorter values for whole-brain RT (WBRT) + anlotinib group, WBRT + LCRT + anlotinib group, WBRT, and WBRT + LCRT. Conclusion: Anlotinib can improve the intracranial lesion control and survival prognosis of NSCLC patients with CRT.

4.
BMC Nurs ; 20(1): 123, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233678

RESUMO

BACKGROUND: Fear of workplace violence has become a critical issue worldwide, which can lead to burnout, low levels of job satisfaction, and turnover. However, to date, little attention has been directed toward fear of workplace violence among nurses. Accordingly, this study investigated the level of fear of future workplace violence and its influencing factors among nurses in Shandong, China. METHODS: A cross-sectional study was conducted from July 30 through September 30, 2020 in Shandong Province, China. A total of 1898 nurses were enrolled from 12 tertiary hospitals. Fear of future workplace violence was measured using the Fear of Future Violence at Work scale. Demographic information, employment characteristics, social support, and experience of workplace violence were assessed. Multiple linear regression analysis was used to explore the influencing factors of fear of future workplace violence. RESULTS: The average score of fear of future violence at work was 67.43 ± 17.20 among nurses. Multiple linear regression analysis showed that higher fear of future violence at work scores were reported among nurses who were female (B = 7.10, p < 0.001), married (B = 3.50, p = 0.028), with a monthly income ≥5000 Chinese yuan (CNY) (B = 3.14, p = 0.007), working in the department of internal medicine (B = 2.90, p = 0.032), surgery (B = 5.03, p < 0.001), pediatrics (B = 5.38, p = 0.003), or emergency department (B = 4.50, p = 0.010), working as a contract employee (B = 2.41, p = 0.042), or who had experienced workplace violence (B = 7.02, p < 0.001). Lower fear of future violence at work scores were found among nurses who took vacations (1-14 days: B = - 2.52, p = 0.047; ≥15 days: B = - 3.69, p = 0.007) and had a high-level of social support (B = - 2.03, p = 0.020). CONCLUSIONS: There was a high level of fear of future workplace violence among nurses in Shandong, China. This should be considered an important issue by hospital administrators and government officials. Effective interventions need to be enacted to address the influencing factors of fear of future workplace violence.

5.
J Affect Disord ; 293: 29-35, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34166906

RESUMO

BACKGROUND: Fear of future workplace violence has adverse effects on nurses' health outcomes. However, the association between fear of future workplace violence and burnout among nurses in China remains unknown. METHODS: Enrolled in the study were 1897 nurses from 12 tertiary hospitals of Shandong Province, China. Fear of future workplace violence was measured using the Fear of Future Violence at Work scale. Burnout was measured using the 15-item Maslach Burnout Service Inventory. Ordinal logistic regression analysis was used to examine the association between fear of future workplace violence and burnout. RESULTS: The prevalence of high emotional exhaustion, high cynicism, and low personal accomplishment was 26.7%, 38.1%, and 35.6%, respectively, while 72.9% of participants had high levels of fear of future workplace violence. Among nurses, compared with high levels of fear of future workplace violence, low levels of fear were associated with a lower degree of emotional exhaustion, cynicism, and personal accomplishment; and medium levels of fear were associated with a lower degree of emotional exhaustion, cynicism, and a higher degree of personal accomplishment. LIMITATIONS: This was a cross-sectional study, which could not establish the causal relationship between fear of future workplace violence and burnout. CONCLUSION: There was a significant association between fear of future workplace violence and burnout among nurses. Fear of future workplace violence should be regarded as important issue for hospital administrators and healthcare policy makers when taking measures to ameliorate nurses' burnout.


Assuntos
Esgotamento Profissional , Enfermeiras e Enfermeiros , Violência no Trabalho , Esgotamento Profissional/epidemiologia , China/epidemiologia , Estudos Transversais , Medo , Humanos , Inquéritos e Questionários
6.
Dev Comp Immunol ; 124: 104185, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34174243

RESUMO

Circular RNAs (circRNAs), a class of non-coding RNAs, play an important role in regulating various biological processes. In the present study, circRNAs from the Megalobrama amblycephala liver were identified at five different time points post Aeromonas hydrophila using RNA-seq technology. A total of 250 circRNAs were identified, of which 106 were differentially expressed (DE) in ten pairwise comparisons. GO and KEGG analyses showed that the parental genes of DE circRNAs were enriched in phagocytosis, complement and coagulation cascades, and Fc gamma R-mediated phagocytosis pathways. According to ceRNA hypothesis, the interaction network of circRNAs, miRNAs and mRNAs was constructed. Moreover, WGCNA was conducted, and five specific modules significantly related to bacterial infection were identified. All the above results reveal the important role of circRNAs in immune response, which enriches the information of circRNAs in teleost, and helps to understand the immune response mechanism of M. amblycephala to A. hydrophila.

7.
Oncol Rep ; 45(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33864661

RESUMO

The present study aimed to investigate the role of partner of NOB1 homolog (PNO1) in esophageal cancer (EC). The expression levels of PNO1 in EC were primarily analyzed using data obtained from databases. PNO1 expression was also knocked down in EC cells (Eca­109 and TE1) to determine the biological effects of PNO1 on tumorigenesis in vitro and in vivo. In addition, possible downstream targets of PNO1 in EC were identified. The expression levels of PNO1 were upregulated in the tumor tissues compared with that noted in normal tissues. Moreover, the knockdown (KD) of PNO1 suppressed cell proliferation, migration and invasion, and promoted cell apoptosis (P < 0.05). Furthermore, the protein expression levels of AKT1, Twist, Myc, mTOR, matrix metalloproteinase 2 (MMP2), nuclear factor (NF)­κB p65 and ß­catenin 1 (CTNNB1) were downregulated following the KD of PNO1 in Eca­109 cells (P < 0.05). In addition, the overexpression of CTNNB1 reversed the effects of PNO1 KD in Eca­109 cells (P < 0.05). In conclusion, the findings of the present study suggest that PNO1 promotes EC progression by regulating AKT1, Twist, Myc, mTOR, MMP2, NF­κB p65 and CTNNB1 expression.

8.
BMC Psychiatry ; 21(1): 217, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926402

RESUMO

BACKGROUND: Social support is an important factor for individual's mental health. However, the association between social support and depressive symptoms among physicians in China' tertiary hospitals has not been explored. This study aimed to investigate its association among physicians stratifying by sex. METHODS: Six hundred fifty-six physicians were enrolled from 12 tertiary hospitals of Shandong Province, China. Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale. Social support was evaluated using the Social Support Rating Scale. Multiple linear regression analysis was used to examine the relationship between social support and depressive symptoms among physicians. RESULTS: The prevalence of depressive symptoms was 42.3% and the average social support score was 38.82 ± 7.53 among physicians. Lower subjective social support scores (male: ß = - 0.317, p < 0.001; female: ß = - 0.241, p < 0.001) and lower objective social support scores (male: ß = - 0.218, p = 0.038; female: ß = - 0.277, p = 0.035) were associated with high depressive symptoms among physicians. Lower support utilization scores (ß = - 0.472, p < 0.001) were associated with high depressive symptoms among male physicians. CONCLUSIONS: Chinese physicians had a higher prevalence of depressive symptoms and lower social support than the Chinese general population. Objective and subjective social support were inversely associated with depressive symptoms among male and female physicians while support utilization was inversely associated with depressive symptoms among male rather than female physicians. It is critical to improve physicians' mental health through strengthening social support in China.


Assuntos
Depressão , Médicos , China/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Masculino , Prevalência , Apoio Social , Inquéritos e Questionários , Centros de Atenção Terciária
9.
BMC Gastroenterol ; 21(1): 103, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663400

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a major cancer burden, and prognosis is determined by many demographic and clinicopathologic factors. The present study aimed to construct a prognostic nomogram for colorectal cancer patients with distant metastasis. METHODS: Colorectal cancer patients with distant metastasis diagnosed between 2010 and 2016 were selected from the Surveillance, Epidemiology, and End Results database. Cox proportional hazards regression was used to identify independent prognostic factors. A nomogram was constructed to predict survival, and validation was performed. RESULTS: A total of 7099 stage IV colorectal cancer patients were enrolled in the construction cohort. The median overall survival was 20.0 (95% CI 19.3-20.7) months. Age at diagnosis, marital status, race, primary tumour site, tumour grade, CEA level, T stage, N stage, presence of bone, brain, liver and lung metastasis, surgery for primary site and performance of chemotherapy were independent prognostic factors. The nomogram was constructed and the calibration curve showed satisfactory agreement. The C-index was 0.742 (95% CI 0.726-0.758). In the validation cohort (7098 patients), the nomogram showed satisfactory discrimination and calibration with a C-index of 0.746 (95% CI 0.730-0.762). CONCLUSION: A series of factors associated with the survival of CRC patients with distant metastasis were found. Based on the identified factors, a nomogram was generated to predict the survival of stage IV colorectal cancer patients. The predictive model showed satisfactory discrimination and calibration, which can provide a reference for survival estimation and individualized treatment decisions.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Colorretais/patologia , Humanos , Estadiamento de Neoplasias , Nomogramas , Prognóstico
10.
Aging (Albany NY) ; 13(3): 4552-4563, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33495422

RESUMO

INTRODUCTION: We investigated cognitive function and its influencing factors in empty-nest and non-empty-nest elderly adults in China. RESULTS: Cognitive function was better in empty-nest elderly living as a couple but worse in those living alone than in non-empty-nest elderly. Older age, rural habitation, poorer instrumental activities of daily living, and depression were risk factors for cognitive decline, while higher education was protective. Women had poorer cognitive function than men among non-empty-nest elderly and empty-nest elderly living as a couple. Among non-empty-nest elderly, those who were divorced/widowed/never married, underweight or economically active exhibited poorer cognitive function. Having two or more chronic diseases and being overweight were associated with better cognitive function among empty-nest elderly living as a couple. CONCLUSION: These findings suggest that cognitive function is poorest in empty-nest elderly living alone and best in empty-nest elderly living as a couple. The factors influencing cognitive function differed according to empty-nest status, which should be considered in interventions. METHODS: 5549 elderly from the 2015 China Health and Retirement Longitudinal Study were included in this study. Cognitive function was evaluated using the Telephone Interview for Cognitive Status, episodic memory tests and visuospatial ability assessments. Factors influencing cognitive function were determined via multiple linear regression analysis.


Assuntos
Cognição , Disfunção Cognitiva/epidemiologia , Depressão/epidemiologia , Características da Família , Sobrepeso/epidemiologia , Magreza/epidemiologia , Atividades Cotidianas , Fatores Etários , Idoso , China/epidemiologia , Escolaridade , Feminino , Estado Funcional , Humanos , Masculino , Estado Civil/estatística & dados numéricos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de Proteção , Características de Residência , Fatores de Risco , População Rural/estatística & dados numéricos , Fatores Sexuais
11.
Acta Neurochir (Wien) ; 163(2): 521-529, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33219865

RESUMO

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are a type of soft tissue sarcomas (STS) with recurrence and metastatic potential. We aimed to investigate the risk factors for developing distant metastases (DM) and to identify the prognostic factors in patients with DM. METHODS: Based on the Surveillance, Epidemiology, and End Result (SEER) database, MPNST patients diagnosed between 2010 and 2016 were extracted in our study. The logistic regression model was performed for predicting DM development while the Cox proportional hazard regression model was conducted for revealing the prognostic factors. RESULTS: Eventually, 764 patients diagnosed with MPNSTs were included with 109 cases presenting with metastases at initial diagnosis. Larger tumor size and lymph node metastases were independent risk factors for developing DM. The median overall survival (OS) for patients with metastases was 8.0 (95% CI: 6.1-9.9) months. Multiple metastatic sites and no surgical treatment were prognostic factors for worse survival. Tumors located in non-head and neck region were related with better survival. CONCLUSIONS: The incidence of DM was 14.3% with a dismal median OS of 8.0 months for metastatic MPNSTs. More evaluation should be applied for patients with large tumor size and lymph metastases. Tumors located in head and neck region and the presence of multiple metastases predicted worse survival outcome. Surgical treatment can significantly improve the survival of MPNST patients with distant metastasis.


Assuntos
Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/patologia , Neurofibrossarcoma/epidemiologia , Neurofibrossarcoma/secundário , Neoplasias de Tecidos Moles/epidemiologia , Neoplasias de Tecidos Moles/patologia , Adulto , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/enzimologia , Neurofibrossarcoma/mortalidade , Prognóstico , Fatores de Risco , Programa de SEER , Neoplasias de Tecidos Moles/mortalidade , Estados Unidos/epidemiologia , Adulto Jovem
12.
Orthop Surg ; 13(1): 134-144, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33305494

RESUMO

OBJECTIVE: The aim of this study was to examine the survival rate of patients with different bone sarcomas and to investigate homogenous and heterogenous prognostic factors for different types of bone sarcomas. METHODS: This is a retrospective analysis of records from the Surveillance, Epidemiology, and End Result (SEER) database. Clear information on the distant metastasis of cancer is provided in the SEER database for patients diagnosed between January 2010 and December 2016. Data for the four types of malignant bone sarcomas were extracted, including osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma. Patients with bone sarcomas originated from other sites, diagnosed at autopsy, or indicated in death certification were excluded. The overall survival was calculated for the entire cohort and across different bone sarcomas using the Kaplan-Meier method. A subgroup analysis of the different survival rates of four types of bone sarcomas in various levels of each variable was conducted and the differences were tested with the log-rank test. Cox proportional hazard regression analysis was performed to determine the prognostic factors. Variables with P < 0.05 in the univariate Cox regression analysis were further analyzed using a multivariate Cox regression analysis. The prognostic factors in four groups of bone sarcomas were compared to determine the homogenous and heterogenous factors. RESULTS: A total of 4732 patients were included with a follow up of 25 (0-83) months. The mean age of patients was 39.7 ± 24.1 years. The 1-year, 3-year, and 5-year overall survival rate for the entire cohort was 86.2% (95% confidence interval [CI]: 85.2%-87.2%), 70.5% (95% CI: 68.9%-72.1%), and 63.0% (95% CI: 61.2%-64.8%), respectively. Factors including age older than 40 years, higher grade, regional and distant stage, tumor in the extremities, T2 stage, bone and lung metastases, and non-surgery were significantly associated with the poor survival of the entire cohort. The mean overall survival duration of patients with chordoma, chondrosarcoma, Ewing sarcoma, and osteosarcoma was 66.86 (95% CI: 64.06-69.66), 63.53 (95% CI: 61.81-65.25), 58.06 (95% CI: 55.49-60.62) and 54.91 (95% CI: 53.14-56.69) months, respectively. Compared with chordoma, the hazard ratio (HR) and 95% CI for patients with chondrosarcoma, Ewing sarcoma, and osteosarcoma were 1.30 (95% CI: 1.04-1.62; P = 0.023), 1.69 (95% CI: 1.33-2.14; P < 0.001), and 2.00 (95% CI: 1.61-2.48; P <0.001), respectively. Different bone sarcomas showed homogenous and heterogenous prognostic factors. CONCLUSION: Different clinicopathological characteristics and prognoses were revealed in patients with osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma. The risk factors can potentially guide prognostic prediction and sarcoma-specific treatment.

13.
J Sci Food Agric ; 101(1): 82-90, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32608134

RESUMO

BACKGROUND: Early weaning in yak calves is being attempted to improve yak reproduction rate. However, this has to be done with caution because of the high mortality rate of calves due to the lack of nutrients and the harsh environmental conditions. Twenty-four weaned male yak calves were used in a 60 day feeding trial in which astragalus root extract (ARE) was supplemented. They were assigned randomly to one of four dietary treatments (n = six per treatment) that differed in ARE level: 0 g kg-1 (control), ARE0 ; 20 g kg-1 , ARE20 ; 50 g kg-1 , ARE50; and 80 g kg-1 dry matter intake (DMI), ARE80 . RESULTS: Final bodyweight and average daily gain (ADG) were significantly higher and the DMI/ADG ratio was significantly lower in calves with ARE supplementation than control (ARE0 ) calves. Ruminal concentrations of acetate and propionate and serum concentration of superoxide dismutase in ARE80 calves were higher than in the other groups and serum concentration of insulin was higher in ARE80 calves than in ARE20 calves. Serum immunoglobulin G (IgG) and interleukin-2 (IL-2) concentrations in ARE-fed calves were higher than in controls. Serum tumor necrosis factor (TNF-α) concentration was higher in ARE50 and ARE80 groups than ARE0 calves and serum interleukin-6 (IL-6) concentration was higher in ARE80 than in ARE0 calves. Serum immunoglobulin A (IgA), IgG and immunoglobulin M (IgM) concentrations increased with age in ARE-fed calves. ARE supplementation increased the abundance of fiber degrading bacteria. CONCLUSION: ARE at a dosage of 5% to 8% DMI can be supplemented to early weaned yak calves to improve growth performance, antioxidant capacity and immunity. © 2020 Society of Chemical Industry.


Assuntos
Ração Animal/análise , Astrágalo (Planta)/metabolismo , Bovinos/crescimento & desenvolvimento , Bovinos/imunologia , Microbioma Gastrointestinal , Animais , Antioxidantes/metabolismo , Astrágalo (Planta)/química , Bovinos/metabolismo , Bovinos/microbiologia , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Masculino , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Rúmen/metabolismo , Rúmen/microbiologia
14.
Stem Cell Reports ; 15(4): 968-982, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-33053361

RESUMO

Sertoli cells are the major component of the spermatogonial stem cell (SSC) niche; however, regulatory mechanisms in Sertoli cells that dictate SSC fate decisions remain largely unknown. Here we revealed features of the N6-methyladenosine (m6A) mRNA modification in Sertoli cells and demonstrated the functions of WTAP, the key subunit of the m6A methyltransferase complex in spermatogenesis. m6A-sequencing analysis identified 21,909 m6A sites from 15,365 putative m6A-enriched transcripts within 6,122 genes, including many Sertoli cell-specific genes. Conditional deletion of Wtap in Sertoli cells resulted in sterility and the progressive loss of the SSC population. RNA sequencing and ribosome nascent-chain complex-bound mRNA sequencing analyses suggested that alternative splicing events of transcripts encoding SSC niche factors were sharply altered and translation of these transcripts were severely dysregulated by Wtap deletion. Collectively, this study uncovers a novel regulatory mechanism of the SSC niche and provide insights into molecular interactions between stem cells and their cognate niches in mammals.

15.
Clin Cancer Res ; 26(24): 6445-6452, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33046518

RESUMO

PURPOSE: Patients with alveolar soft part sarcoma (ASPS) are rare and have few treatment options. We assessed the activity of geptanolimab (GB226), a fully humanized programmed cell death protein 1 antibody, for patients with unresectable, recurrent, or metastatic ASPS. PATIENTS AND METHODS: We conducted this multicenter, single-arm, phase II study (Gxplore-005, NCT03623581) in patients aged 18-75 years who had unresectable, recurrent, or metastatic ASPS at 11 sites in China. Patients received intravenous geptanolimab (3 mg/kg) every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed by independent review committee (IRC) per RECIST 1.1 in the full analysis set population. RESULTS: Between September 6, 2018 and March 6, 2019, we enrolled and treated 37 patients with 23 (62.2%) having received prior systemic treatment. Fourteen [37.8%; 95% confidence interval (CI), 22.5-55.2] of 37 patients had an objective response assessed by IRC with a 6-month duration of response rate of 91.7%. Median progression-free survival was 6.9 months (95% CI, 5.0-not reached) and disease control was achieved in 32 (86.5%; 95% CI, 71.2-95.5) patients. Three of 37 patients reported grade 3 treatment-related adverse events (TRAEs), including anemia, hypophysitis, and proteinuria [one each (2.7%)]. No grade 4 TRAEs were observed. Two (5.4%) patients discontinued treatment due to TRAEs (one with hypophysitis and one with Mobitz type I atrioventricular block). The baseline percentage of CD4+ T cells was adversely associated with patient response (P = 0.031). CONCLUSIONS: Geptanolimab has clinically meaningful activity and a manageable safety profile in unresectable, recurrent, or metastatic ASPS.

16.
Aging (Albany NY) ; 12(16): 16046-16061, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32889800

RESUMO

We aimed to perform a pan-metastatic cancer analysis on survival and prognostic factors and to create a prognosis-based classification system. We selected distant metastasis patients from the Surveillance, Epidemiology, and End Results (SEER) database. The associations between the characteristics of the patients at admission and overall survival were determined. A prognosis-based metastatic cancer classification was established based on the identified prognostic factors. The differences in prognosis among these categories were tested. The survival rate and prognostic factors were not consistent across cancers. Three metastatic cancer categories were generated, each with different prognoses. The prognostic differences among the categories were satisfactorily validated. Different metastatic cancer types had homogeneous and heterogeneous survival rates and prognostic factors. A prognosis-based classification system for synchronous distant metastasis cancer patients at admission was created. This classification system reflects the grade of malignancy in metastatic cancers and may guide the prediction of survival and individualized treatment. Moreover, it may have important implications for the management of synchronous metastatic cancers and aid clinicians in properly allocating medical resources to metastatic patients.


Assuntos
Técnicas de Apoio para a Decisão , Neoplasias/classificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Tomada de Decisão Clínica , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias/mortalidade , Neoplasias/patologia , Neoplasias/terapia , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Programa de SEER , Estados Unidos/epidemiologia , Adulto Jovem
17.
J Cancer ; 11(18): 5359-5370, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742482

RESUMO

Objectives: The present study aimed to evaluate the early mortality rate and associated factors for early death in bone and soft tissue tumors, and to construct predictive nomogram. Methods: Patients diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) dataset were enrolled. The early death (survival time ≤ 3 months) rate was calculated and associated risk factors were evaluated by the logistic regression models. The significant factors were used to construct predictive nomograms. Results: A total of 2,003 (8.5%) patients died within 3 months after cancer diagnosis, among whom 1,146 (4.9%) patients died from cancer-specific cause. Older age (19-50 and >50 years), grade (III and IV), reginal or distant stage were associated with higher odds of total, cancer-specific and non-cancer-specific early death. T2 stage, metastasis to brain and lung were risk factors for total and cancer-specific early death. Surgical interventions significantly decreased the odds of total, cancer-specific and non-cancer-specific early death. Female and black race were associated with lower odds of non-cancer-specific early death. The area under the curve (AUC) of the nomograms for total early death, cancer-specific and non-cancer-specific early death prediction was 88.0%, 89.0% and 83.2%, respectively. Conclusions: A total of 8.5% patients with bone and soft tissue tumors suffered early death. Several risk factors were associated with higher odds of early death while surgery can decrease the possibility of early death. Nomograms based on all related factors can be used to estimate the early death in bone and soft tissue tumors.

18.
BMC Cancer ; 20(1): 756, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787801

RESUMO

BACKGROUND: Prognosis is poor for patients with malignant progression such as distant metastasis of oral squamous cell carcinoma (OSCC). Evidence indicates that miR-448 promotes the proliferation and inhibits apoptosis of OSCC cells. Therefore, we aimed to investigate the function of miR-448 to predict tumor progression and prognosis of OSCC. METHODS: Real-time quantitative reverse transcription PCR was used to measure miR-448 expression in 221 pairs of OSCC tissues and the corresponding noncancerous tissues. Patients were diagnosed with OSCC from 2009 through 2011 at the Tianjin Medical University Cancer Institute and Hospital. Chi-squared tests were performed to assess the associations between miR-448 expression and clinicopathological parameters. Kaplan-Meier analysis was employed to evaluate the association of overall survival (OS) and disease-free survival (DFS) with miR-448 levels. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. RESULTS: We show here that miR-448 expression was significantly up-regulated in OSCC tissues compared with noncancerous tissues (P < 0.01). High miR-448 expression was significantly associated with advanced T stage (P = 0.001), lymph node metastasis (P = 0.007) and higher TNM stage (P = 0.009). Moreover, Kaplan-Meier and univariate analyses revealed that patients with high expression of miR-448 experienced significantly shorter OS and DFS. Furthermore, multivariate analysis demonstrated that miR-448 expression was an independent prognostic factor for OS (P = 0.004) and DFS (P = 0.002). CONCLUSIONS: Our present data suggests that miR-448 may play an important role in tumor progression and serves as a prognostic marker for OSCC. Further studies are required to assess the potential value of miR-448 to contribute to personalized treatment of OSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , MicroRNAs/metabolismo , Neoplasias Bucais/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Proliferação de Células , Distribuição de Qui-Quadrado , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Prognóstico , Modelos de Riscos Proporcionais , Regulação para Cima
19.
Med Sci Monit ; 26: e925169, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32705998

RESUMO

BACKGROUND Spinal metastases can cause metastatic epidural spinal cord compression (MESCC), which can result in neurological dysfunction and impaired quality of life. This study investigated the safety and effectiveness of posterior decompression surgery and radiofrequency ablation followed by vertebroplasty in spinal metastasis from lung cancer. MATERIAL AND METHODS From June 2008 to September 2015, a retrospective analysis was conducted in 15 patients with spinal metastasis from lung cancer. All cases suffered MESCC and underwent posterior decompression surgery to relieve the compression of spinal cord, and had radiofrequency ablation followed by vertebroplasty. All patients received postoperative multidisciplinary therapy. The operative time, blood loss, complications, pain, neurologic deficit, quality of life, and survival were assessed preoperatively and postoperatively. RESULTS Patients were followed from 6 to 56 months. The mean time of operation was 154±50 minutes and the mean blood loss was 210±90 mL. In the pre-operation analysis found the mean visual analogue scale (VAS) was 7.86±0.86. In the post-operation analysis at 3 months, the mean VAS score was 3.51±1.32. The VAS improved significantly (t=7.95, P<0.01). The Frankel grade was improved 1 grade or 2 grades in 14 patients when pre-operation was compared to post-operation. Only 1 patient kept Frankel grade D after surgery. Eight patients with sphincteric dysfunction preoperatively were improved after surgery. The EORTC QLQ-C30 score was 86.13±8.51 preoperatively and 52.21±13.28 postoperatively. The quality of life was improved significantly (t=11.8, P<0.01). The median survival time was 11 months. CONCLUSIONS Through posterior decompression surgery and radiofrequency ablation followed by vertebroplasty, the quality of life was improved significantly. This palliative treatment was effective and safe in spinal metastasis from lung cancer.


Assuntos
Descompressão Cirúrgica/métodos , Ablação por Radiofrequência/métodos , Compressão da Medula Espinal/cirurgia , Adulto , Idoso , Espaço Epidural , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Dor , Medição da Dor , Período Pós-Operatório , Qualidade de Vida , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/cirurgia , Vértebras Torácicas/cirurgia , Vertebroplastia/métodos , Escala Visual Analógica
20.
Am J Transl Res ; 12(5): 2071-2082, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509201

RESUMO

BACKGROUND: The distant metastasis in liposarcoma is not thoroughly investigated. Based on a large cohort, we attempted to evaluate the survival in liposarcoma patients with distant metastasis and to reveal the risk factors. METHODS: The records of liposarcoma patients with or without distant metastasis were extracted from the Surveillance, Epidemiology, and End Result (SEER) database from 2010 to 2016. Survival was calculated by the Kaplan-Meier method. Cox hazard regression was scheduled to investigate prognostic factors for liposarcoma patients with distant metastasis. Risk factors for metastasis were identified by the logistic regression analysis. RESULTS: A total of 227 liposarcomas with distant metastasis were identified in 4,181 patients. The 5-year survival rate for patients with and without metastasis was 12.1% (95% CI: 5.0%-19.0%) and 75.4% (95% CI: 73.6%-77.2%), respectively. Age ≥60 years (HR=1.73; 95% CI: 1.11-2.69) and surgery (HR=0.26; 95% CI: 0.17-0.41) were independent prognostic factors for patients with metastasis. The annual incidence of distant metastasis was from 3.76% to 7.3%. Liposarcoma in trunk (OR=1.69; 95% CI: 1.02-2.79), myxoid type (OR=2.65; 95% CI: 1.16-6.05), grade III (OR=2.62; 95% CI: 1.17-5.88), grade IV (OR=4.07; 95% CI: 1.84-9.00), T2 stage (OR=2.71; 95% CI: 1.15-6.40), and N1 stage (OR=9.44; 95% CI: 4.63-19.26) were associated with the development of metastasis. Homogeneous and heterogeneous factors were found for patients with different metastatic organs. CONCLUSIONS: The survival was significantly dismal in liposarcoma patients with distant metastasis. The risk and prognostic factors provide a reference to clinical screening and prevention for distant metastasis in liposarcoma.

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