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1.
Int Orthop ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34647137

RESUMO

PURPOSE: To summarize the evolution of Ilizarov technology in China, highlight important milestones, introduce the atmosphere of the era concerning the first uses and development of this technology, and share Chinese modification and experience in this field. METHOD: A thorough interview with senior ASAMI members of China and literature search and physical books in libraries was undertaken to summarize the history of Ilizarov technology in China. RESULTS: The formal development of Ilizarov technology began when professor Ilizarov himself came to Beijing (1991) and gave a speech. In the following 31 years, his technology was rapidly developed through China, with many symposiums held and associations established including ASAMI China (2003) and ILLRS China (2015). Today, Ilizarov technology has become the main treatment of complex fractures, defects, nonunion, infections, deformities, and chronic ischemic ulcers of the limbs. In those years, Chinese scholars also developed some special treatment methods and made many modifications to Ilizarov external fixators. CONCLUSION: Ilizarov technology has developed in China for 31 years. It revolutionized the treatment of complex limb traumas, deformities, and diseases. In the treatment of millions of patients, Chinese scholars had many unique experiences and made modifications to this technology which is worthy to share with the world.

2.
Int J Biol Sci ; 17(13): 3508-3521, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512162

RESUMO

Rationale: The malignant phenotypes of glioblastomas (GBMs) are primarily attributed to glioma stem cells (GSCs). Our previous study and other reports have suggested that both miR-139 and its host gene PDE2A are putative antitumor genes in various cancers. The aim of this study was to investigate the roles and mechanisms of miR-139/PDE2A in GSC modulation. Methods: Clinical samples were used to determine miR-139/PDE2A expression. Patient-derived glioma stem-like cells (PD-GSCs) were stimulated for immunofluorescent staining, sphere formation assays and orthotopic GBM xenograft models. Bioinformatic analysis and further in vitro experiments demonstrated the downstream molecular mechanisms of miR-139 and PDE2A. OX26/CTX-conjugated PEGylated liposome (OCP) was constructed to deliver miR-139 or PDE2A into glioma tissue specifically. Results: We demonstrated that miR-139 was concomitantly transcribed with its host gene PDE2A. Both PDE2A and miR-139 indicated better prognosis of gliomas and were inversely correlated with GSC stemness. PDE2A or miR-139 overexpression suppressed the stemness of PD-GSCs. FZD3 and ß-catenin, which induced Wnt/ß-catenin signaling activation, were identified as targets of miR-139 and mediated the effects of miR-139 on GSCs. Meanwhile, PDE2A suppressed Wnt/ß-catenin signaling by inhibiting cAMP accumulation and GSK-3ß phosphorylation, thereby modulating the self-renewal of PD-GSCs. Notably, Notch1, which is also a target of miR-139, suppressed PDE2A/miR-139 expression directly via downstream Hes1, indicating that miR-139 promoted its own expression by the miR-139-Notch1/Hes1 feedback circuit. Expectedly, targeted overexpression miR-139 or PDE2A in glioma with OCP system significantly repressed the stemness and decelerated glioma progression. Conclusions: Our findings elaborate on the inhibitory functions of PDE2A and miR-139 on GSC stemness and tumorigenesis, which may provide new prognostic markers and therapeutic targets for GBMs.

3.
BMJ Open ; 11(8): e045417, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34341036

RESUMO

OBJECTIVES: To evaluate the long-term survival outcomes and adverse effects of intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) and to summarise the experiences of IMRT in NPC in the past few decades in non-endemic northwest China. DESIGN: A population-based retrospective study. SETTING: An experience of using IMRT in non-endemic region of China. PARTICIPANTS: The study included 792 newly diagnosed and non-metastatic NPC patients who received IMRT from January 2006 to September 2018 in Xijing Hospital. OUTCOME MEASURES: The survival outcomes, adverse effects and failure patterns were evaluated by univariate, multivariate and subgroup analyses. RESULTS: With a median follow-up time of 46.2 months, the 5-year local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, disease-free survival (DFS) and overall survival (OS) rates were 90.8%, 97.0%, 82.8%, 69.6% and 78.0%, respectively. Multivariate analysis showed that age, N stage, clinical stage, pathological type and primary tumour volume of more than 23 cm3 were the independent prognosis factors for DFS (all p<0.05); age, N stage, pathological type, cervical lymph node necrosis, and anaemia were significantly associated with OS (all p<0.05). The most common acute toxicities of IMRT were dermatitis, mucositis and dysphagia. Xerostomia and hearing impairment were the top two late toxicities. The main failure patterns were distant metastasis and local and/or regional relapses. CONCLUSIONS: Similar survival, toxicities and failure patterns have been observed in patients treated with IMRT in a non-endemic area of China when compared with that in endemic areas. Induction chemotherapy combined with concurrent chemoradiotherapy may benefit locally advanced NPC in non-endemic areas of China.


Assuntos
Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Quimiorradioterapia , China/epidemiologia , Intervalo Livre de Doença , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Estadiamento de Neoplasias , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
4.
Lancet ; 398(10297): 303-313, 2021 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-34111416

RESUMO

BACKGROUND: Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18-65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III-IVA, excluding T3-4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12-16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m2 body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111. FINDINGS: Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33-42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4-90·6]) than in the standard therapy group (75·7% [69·9-81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32-0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group. INTERPRETATION: The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma. FUNDING: The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Capecitabina/administração & dosagem , Quimioterapia Adjuvante/métodos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Administração Metronômica , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Radiat Oncol ; 16(1): 118, 2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34176495

RESUMO

BACKGROUND: Cranial nerve (CN) palsy due to cancer involvement has been considered as an unfavorable prognostic factor for patients with nasopharyngeal carcinoma (NPC). We assessed the role of IMRT based treatment on the recovery of CN palsy and investigated the prognostic value of complete recovery of CN palsy. METHODS: A total of 115 NPC patients with cancer-related CN palsy were included in the study. We referred CTCAE version 5.0 to evaluate the grade of CN palsy. RESULTS: All patients with grade 1 CN palsy recovered completely during the 2 years of follow-up after definite treatment. Most grade 2 palsy could change gradually to grade 1 palsy or complete recovery during 2 years of follow-up. Patients with more than 2 symptoms of CN palsy had poor 3-year disease-free survival (DFS) than these with 1 or 2 symptoms (60.3% vs. 84.9%, HR 0.25, 95% CI 0.07-0.89, P = 0.001). There were no significant differences for PFS, OS, DMFS and LRFS between patients with complete recovery and non-complete recovery from CN palsy after receiving IMRT based comprehensive treatment. CONCLUSIONS: IMRT based comprehensive treatment could effectively promote the recovery of tumor-related CN palsy for NPC patient. More than 2 symptoms of CN palsy was a poor prognostic factor for DFS of NPC patients. The prognostic role of complete recovery of CN palsy was not identified in our study.

6.
J Environ Manage ; 280: 111639, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33203578

RESUMO

This study investigated an innovative decentralized water system which combined rainwater harvesting with wastewater reclamation to generate 39% of the water resources needed for a higher education institution with student and staff accommodation in India. We collected performance data to critically appraise the current water system, design alternatives and water management optimization opportunities. The campus was recently built in a hot, semi-arid region of India with a summer, monsoon and winter season. It represented in a microcosm the vision of leading Indian engineers for a more sustainable urban systems future. We collated the water infrastructure costs, blue and recycled water demands, chemical demands, electricity demands and operational costs over a calendar year. The annual institutional water demand was 379,768 m3, of which 32% was sourced from reclaimed wastewater, and 7% from roof-collected rainwater. Electricity consumption was 0.40 kWh/m3 for drinking water treatment, and 0.62 kWh/m3 for wastewater treatment, in line with median values reported for centralized systems. Rainwater harvesting and wastewater reclamation accounted for 42% of the water infrastructure costs, with a predicted payback period of >250 years through reduced operational costs. Scenario analysis recommended a water system design alternative with wastewater reclamation for ground maintenance only, which was predicted to yield similar environmental benefits, with an infrastructure cost payback period of only 15 years. Scenario analysis also revealed how better water management to address leakage, and more drought-tolerant landscaping, could improve environmental metrics of the current system by up to 52% and reduce operational costs by up to 23%. Reducing high domestic water usage was found to be essential to secure gains achieved with water infrastructure innovations. Rainwater harvesting had high infrastructure costs, and water policy in low- and middle-income countries should instead support wastewater reclamation and best practice in water management.


Assuntos
Águas Residuárias , Purificação da Água , Conservação dos Recursos Naturais , Humanos , Índia , Chuva , Água , Abastecimento de Água
7.
Medicine (Baltimore) ; 99(51): e23770, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371143

RESUMO

ABSTRACT: Laryngeal tuberculosis (LTB) is highly contagious and can cause permanent laryngeal damage. Therefore, correctly identifying laryngoscopic LTB lesion locations, sizes, and morphologic features are essential for LTB diagnoses. This study aimed to explore the appearance and morphologic features of LTB and correlated these features with clinical symptoms.We retrospectively analysed 39 LTB patients in our hospital between January 2013 and December 2019. Medical records, including clinical presentation, lesion appearance (locations, sizes, and morphology), complementary examination results, and histopathologic features were summarized and analysed.In this patient cohort, dysphonia and sore throat were the two most common clinical symptoms. In LTB patients with extensive lesions, ulcerative lesions were most common, and the proportion of cases with concurrent pulmonary tuberculosis (86.4%, P = .033) infection was higher, as were the positive rates of sputum smears (72.7%, P = .011) and cultures (86.4%, P = .002) than patients without concurrent pulmonary TB and with more localized and exophytic lesions. The histopathologic features of LTB-related ulcerative lesions included fewer granulomas and more areas with caseous necrosis. These lesions were more likely to have acid-fast bacilli detected with a Ziehl-Neelsen stain than exophytic lesions that rarely showed detectable bacilli.A complete knowledge regarding the visual and morphologic features of LTB on laryngoscopy is needed for the early detection and diagnosis of LTB. Our study revealed the lesion sites, sizes, and morphologic features of LTB. These parameters were also correlated with patient clinical symptoms. Future studies are needed to support and expand the results of this retrospective study.


Assuntos
Laringoscopia/métodos , Tuberculose Laríngea/complicações , Tuberculose Laríngea/fisiopatologia , Adulto , China , Estudos Transversais , Feminino , Rouquidão/etiologia , Humanos , Laringe/patologia , Laringe/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Cell Commun Signal ; 18(1): 135, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32843056

RESUMO

BACKGROUND: Glioma stem cells (GSCs) are glioma cells with stemness and are responsible for a variety of malignant behaviors of glioma. Evidence has shown that signals from tumor microenvironment (TME) enhance stemness of glioma cells. However, identification of the signaling molecules and underlying mechanisms has not been completely elucidated. METHODS: Human samples and glioma cell lines were cultured in vitro to determine the effects of adenovirus (ADV) infection by sphere formation, RT-qPCR, western blotting, FACS and immunofluorescence. For in vivo analysis, mouse intracranial tumor model was applied. Bioinformatics analysis, gene knockdown by siRNA, RT-qPCR and western blotting were applied for further mechanistic studies. RESULTS: Infection of patient-derived glioma cells with ADV increases the formation of tumor spheres. ADV infection upregulated stem cell markers and in turn promoted the capacities of self-renewal and multi-lineage differentiation of the infected tumor spheres. These ADV infected tumor spheres had stronger potential to form xenograft tumors in immune-compromised mice. GSCs formation could be promoted by ADV infection via TLR9, because TLR9 was upregulated after ADV infection, and knockdown of TLR9 reduced ADV-induced GSCs. Consistently, MYD88, as well as total STAT3 and phosphorylated (p-)STAT3, were also upregulated in ADV-induced GSCs. Knockdown of MYD88 or pharmaceutical inhibition of STAT3 attenuated stemness of ADV-induced GSCs. Moreover, we found that ADV infection upregulated lncRNA NEAT1. Knockdown of NEAT1 impaired stemness of ADV-induced GSCs. Lastly, HMGB1, a damage associated molecular pattern (DAMP) that triggers TLR signaling, also upregulated stemness markers in glioma cells. CONCLUSION: ADV, which has been developed as vectors for gene therapy and oncolytic virus, promotes the formation of GSCs via TLR9/NEAT1/STAT3 signaling. Video abstract.

9.
Oncol Lett ; 19(6): 3781-3788, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32382330

RESUMO

Human four-and-a-half LIM domains protein 1 (FHL1) is a member of the FHL protein family, which serves an important role in multiple cellular events by interacting with transcription factors using its cysteine-rich zinc finger motifs. A previous study indicated that FHL1 was downregulated in several types of human cancer and served a role as a tumor suppressive gene. The overexpression of FHL1 inhibited tumor cell proliferation. However, to the best of our knowledge, there is no evidence to confirm whether FHL1 affected glioma growth, and the molecular mechanisms through which FHL1 represses tumor development remain unclear. In the present study, the expression level of FHL1 was determined using immunohistochemical staining in 114 tumor specimens from patients with glioma. The results indicated that FHL1 expression was negatively associated with the pathological grade of gliomas. Furthermore, Kaplan-Meier survival curves demonstrated that the patients with an increased FHL1 expression exhibited a significantly longer survival time, suggesting that FHL1 may be a prognostic marker for glioma. The protein level of FHL1 was relatively increased in the U251 glioma cell line compared with that in the U87 cell line. Therefore, FHL1 was knocked down in U251 by siRNA and overexpressed in U87, and it was identified that FHL1 significantly decreased the activation of PI3K/AKT signaling by interacting with AKT. Further experiments verified that FHL1 inhibited the growth of gliomas in vivo by modulating PI3K/AKT signaling. In conclusion, the results of the present study demonstrated that FHL1 suppressed glioma development through PI3K/AKT signaling.

10.
J Cancer Res Clin Oncol ; 146(9): 2369-2378, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32363479

RESUMO

PURPOSE: Although several trials have confirmed the treatment efficacy of induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) from endemic area of China, little is known about the best regime for induction chemotherapy in non-endemic region. This study compared the treatment effect of Gemcitabine and cisplatin (GP) versus docetaxel and cisplatin (TP) followed by concurrent chemoradiotherapy in locoregionally advanced NPC from non-endemic area of China. MATERIALS AND METHODS: A total of 196 locoregionally advanced NPC patients were enrolled in this study, with 142 and 54 patients in TP and GP followed by concurrent chemoradiotherapy groups. The primary endpoint was treatment response of induction chemotherapy. The secondary endpoints included disease-free survival. The Kaplan-Meier method was used to evaluate the efficacy between treatment groups. RESULTS: The median follow-up time was 45.5 months (range: 6-60.5 months). During induction chemotherapy course, GP contributed higher treatment response rate than TP (68.1% vs. 47.1%, p = 0.007). Patients in GP group had better DFS and LRFS than those in TP group (3-year and 5-year DFS, 86.8% and 82.5% vs. 71.7% and 68%, p = 0.036; 3-year and 5-year LRFS, 96.2% and 96.2% vs. 90.5% and 82.8%, p = 0.03). No significant difference of adverse events was observed between two treatment groups in the whole course. CONCLUSION: This study suggested that GP followed by CCRT was better than TP followed by CCRT in improving survival outcomes of locoregionally advanced NPC patients from non-endemic area of China.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Quimiorradioterapia/métodos , China , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel/administração & dosagem , Feminino , Humanos , Quimioterapia de Indução/métodos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Sci Rep ; 10(1): 4155, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139705

RESUMO

Malignant gliomas are the most common tumor in central nervous system with poor prognosis. Due to the limitation of histological classification in earlier diagnosis and individualized medicine, it is necessary to combine the molecular signatures and the pathological characteristics of gliomas. Lots of microRNAs presented abnormal expression in gliomas and modulated gliomas development. Exploration the miRNAs profile is helpful for the diagnosis, therapy and prognosis of gliomas. It has been demonstrated that miR-144 plays important roles in solid tumors. However, the detail mechanisms remained unrevealed. In this study, we have demonstrated the level of miR-144 decreased in glioma tissues from patients, especially in gliomas with higher grades. MiR-144 was also validated have lower expression in glioma cell lines compared with cortical neuron cell by using qRT-PCR. The in vitro functional experiment indicated miR-144 improved gliomas progression through repressing proliferation, sensitizing to chemotherapeutics and inhibiting metastasis. We further identified fibroblast growth factor 7 (FGF7) and Caveolin 2 (CAV2) were target genes of miR-144 by luciferase reporter assay and western blotting. The mechanisms study suggested forced FGF7 expression elevated Akt activation and decreased reactive oxygen species (ROS) generation. The MTT and cell cycle assay indicated miR-144 suppressed glioma cells proliferation through modulating FGF mediated Akt signaling pathway. Meanwhile, miR-144 promoted Temozolomide (TMZ) induced apoptosis in glioma cells via increasing ROS production by using FACS. On the other hand, CAV2, as another target of miR-144, accelerated glioma cells migration and invasion via promoting glioma cells EMT progress. Retrieved expression of FGF7 or CAV2 rescued the proliferation and migration function mediated by miR-144. Furthermore, the in vivo experiments in PDX models displayed the anti-tumor function of miR-144, which could be retrieved by overexpression of FGF7 and CAV2. Taken together, these findings indicated miR-144 acted as a potential target against gliomas progression and uncovered a novel regulatory mechanism, which may provide a new therapeutic strategy and prognostic indicator for gliomas.


Assuntos
Caveolina 2/metabolismo , Fator 7 de Crescimento de Fibroblastos/metabolismo , Glioma/metabolismo , Glioma/patologia , MicroRNAs/metabolismo , Animais , Apoptose/genética , Apoptose/fisiologia , Western Blotting , Caveolina 2/genética , Ciclo Celular/genética , Ciclo Celular/fisiologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Fator 7 de Crescimento de Fibroblastos/genética , Humanos , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Espécies Reativas de Oxigênio/metabolismo
12.
Medicine (Baltimore) ; 99(9): e19361, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118779

RESUMO

Successful reconstruction after tumor resection facilitates rapid recovery and retention of good quality of life, and this is important for a successful operation. This study aimed to analyze and compare the application and efficacy of xenogeneic acellular dermal matrix (xeno-ADM) and abdominal skin graft in hypopharynx reconstruction.This is a retrospective cohort study that included 25 patients with posterior hypopharyngeal wall cancer who underwent partial hypopharyngectomy with laryngeal preservation. The patients were divided into 2 groups according to the repair materials used. Eleven patients were treated with xeno-ADM, and 14 patients with abdominal skin grafts for repairing hypopharyngeal mucosal defects. The intraoperative data, postoperative recovery time of eating function, graft contraction, infection and pharyngeal fistula rate, and 1-year survival rate of the 2 groups were analyzed and compared.Compared with skin grafts group (23.1 ±â€Š5.8 days), the recovery time of eating function in xeno-ADM group was shorter (17.3 ±â€Š6.4 days), (P = .026). Also the number of postoperative hospitalization days were less in the xeno-ADM group (18.5 ±â€Š6.7 days) than in the skin grafts group (24.1 ±â€Š5.6 days) (P = .035). Besides, no significant differences were observed in other comparisons between the 2 groups. Also no obvious rejection and severe graft contraction were observed in both the groups. All patients were successfully decannulated.Both xeno-ADM and abdominal skin grafts demonstrated good effects in the reconstruction of hypopharynx, but the recovery time of eating function in patients with xeno-ADM was faster, which may be due to rapid epithelialization. In addition, it avoids trauma of donor sites.


Assuntos
Derme Acelular/normas , Neoplasias Hipofaríngeas/cirurgia , Complicações Pós-Operatórias/etiologia , Adulto , China , Estudos de Coortes , Feminino , Humanos , Neoplasias Hipofaríngeas/epidemiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Transplante de Pele/métodos , Transplante de Pele/normas
13.
Acta Otolaryngol ; 140(2): 110-115, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31859578

RESUMO

Background: In some cases, there is insufficient external auditory canal (EAC) skin to cover the reconstructed canal wall after canal wall down (CWD) mastoidectomy. Acellular dermal matrix (ADM) can help to repair the skin, mucosa and other epidermal tissue defects.Aims: To investigate the repair effect of xenogeneic ADM (xeno-ADM) for EAC skin defects.Material and Methods: We retrospectively analyzed 28 patients who underwent open mastoidectomy combined with canal wall reconstruction and mastoid obliteration in our hospital. The xeno-ADM was used to repair the EAC skin defect. The epithelialization time, dressing change times, complications and hearing improvement post-operation were summarized and analyzed.Results: Reasons for using xeno-ADM included: 11 (39.3%) cases suffered from extensive middle ear cholesteatoma, three (10.7%) cases suffered from advanced EAC cholesteatoma, eight (28.6%) cases to solve the cavity-related problems, and six (21.4%) patients had a narrow EAC. The postoperative epithelialization time was 5.8 ± 1.6 weeks, and the number of dressing changes was 4.8 ± 1.6 times. There was no xeno-ADM rejection and related complications, the postoperative hearing improvement was statistically significant (p = .013).Conclusions and Significance: Xeno-ADM could be a safe, effective and simple method for repairing skin defect in the reconstruction of EAC after CWD mastoidectomy.


Assuntos
Derme Acelular , Meato Acústico Externo/cirurgia , Mastoidectomia , Reepitelização , Adulto , Idoso , Aloenxertos , Animais , Bovinos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Adulto Jovem
14.
N Engl J Med ; 381(12): 1124-1135, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31150573

RESUMO

BACKGROUND: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials. METHODS: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. RESULTS: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group. CONCLUSIONS: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Adolescente , Adulto , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Análise de Sobrevida , Adulto Jovem
15.
Asian-Australas J Anim Sci ; 32(9): 1414-1422, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30145877

RESUMO

Objective: Two experiments were conducted to determine the effects of adaptation time and inclusion level of sugar beet pulp (SBP) on nutrient digestibility and to evaluate the ileal AA digestibility of SBP fed to pigs. Methods: In Exp. 1, thirty-six crossbred barrows (85.0 ± 2.1 kg) were allotted to 6 diets in a completely randomized design with six replicates per diet. Diets included a corn-soybean meal diet and 5 test diets containing 14.6, 24.4, 34.2, 43.9, or 53.7% SBP, respectively. The adaptation time consisted 7, 14, 21, or 28 d consecutively for each pig followed by 5 d for fecal collection. Feces were collected from d 8 to 13, d 15 to 20, d 22 to 27, and d 29 to 34, respectively. In Exp. 2, six pigs (35.1 ± 1.7 kg) with T-cannulas at the terminal ileum were fed to 3 diets in a replicated 3×3 Latin square design with 3 periods and 2 replicate pigs per diet. Each period consisted 5 d for diet adaptation followed by 2 d for digesta collection. Results: The DE value and the apparent total tract digestibility (ATTD) of GE, DM, ash, and OM in diets linearly decreased (p<0.05) as the adaptation time increased or as the dietary SBP increased, while the ATTD of NDF and ADF in diets linearly increased (p<0.01) as the dietary SBP increased. The DE value and the ATTD of GE and CP in SBP linearly increased (p<0.05) as the adaptation time increased, while the ATTD of CP in SBP linearly decreased (p<0.01) as the inclusion level increased. The SID of Lys, Met, Thr, and Trp in SBP was 37.03, 51.62, 40.68, and 46.22%, respectively. Conclusion: The results of this study indicated that the ATTD of energy and nutrients were decreased as inclusion rate of SBP increased.

16.
Sci Rep ; 8(1): 13318, 2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30190563

RESUMO

Given the potentially distinctive histological variations in northwest of China, the aim of current study was to compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy (IC + CCRT) with concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients with different histological types. A total of 301 patients were included in this study. Patients were classified in two cohorts according to the 2005 WHO World Health Organization histological classification: WHO type IIa group and WHO type IIb group. The Kaplan-Meier method was used to detect the efficacy between IC + CCRT and CCRT in two WHO types cohorts. Propensity score matching method was adopted to balance the baseline covariate and eliminate potential selection bias. On propensity matched analyses, IC + CCRT was found to produce better 3-year DMFS and OS than CCRT in WHO type IIa cohort (DMFS, 76.2% vs. 42.2%, p = 0.029; OS, 78.3% vs. 65.5%, p = 0.027). For WHO type IIb cohort, IC + CCRT was associated with a better 3-year OS (87.4% vs. 77.9%, p = 0.029) and a trend of better 3-year DMFS (85.9% vs. 76%, p = 0.162) compared with CCRT. IC + CCRT was benefit for advanced stage nasopharyngeal carcinoma with different nonkeratinizing carcinoma subtypes.


Assuntos
Quimiorradioterapia , Quimioterapia de Indução , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Estadiamento de Neoplasias , Taxa de Sobrevida
17.
Sci Rep ; 8(1): 13646, 2018 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-30206282

RESUMO

Zearalenone (ZEN) is an estrogen-like mycotoxin occurring in food and feeds, and it can cause oxidative damage and apoptosis in the testis, liver, and kidney. A current concern for researchers is how to reduce the harm it causes to humans and animals. In this study, our aim was to isolate and identify a novel and efficient ZEN-detoxifying strain of bacteria, and we aimed to assess the protective effect of the isolated strain on kidney damage caused by ZEN in mice. Our results indicated that a strain of Bacillus velezensis (B. velezensis), named A2, could completely degrade ZEN (7.45 µg/mL) after three days of incubation at 37 °C in the Luria-Bertani (LB) medium. This fermentation broth of the B. velezensis A2 strain was given to mice. The histopathological analysis indicated that the fermentation broth from the B. velezensis A2 strain reduced the degree of renal injury that is induced by ZEN. Furthermore, it greatly reduced the increase in serum levels of creatinine (CRE), uric acid (UA), and urea nitrogen (BUN) caused by ZEN. In addition, B. velezensis A2 strain also significantly inhibited the increase of malonaldehyde (MDA) content, and reversed the decreases of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities caused by ZEN. Studies have shown that ZEN is involved in the regulation of mRNA and protein levels of genes involved in the ER stress-induced apoptotic pathway, such as heavy chain binding protein (BIP), C-/-EBP homologous protein (CHOP), cysteine Aspartate-specific protease-12 (Caspase-12), c-Jun N-terminal kinase (JNK), and BCL2-related X protein (Bcl-2 and Bax). However, when mice were administered the fermentation broth of the B. velezensis A2 strain, it significantly reversed the expressions of these genes in their kidney tissue. In conclusion, our results indicate that the newly identified strain of B. velezensis A2, has a protective effect from renal injury induced by ZEN in mice. This strain has a potential application in the detoxification of ZEN in feed and protects animals from ZEN poisoning.


Assuntos
Injúria Renal Aguda/metabolismo , Bacillus/metabolismo , Rim/metabolismo , Zearalenona/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/microbiologia , Injúria Renal Aguda/terapia , Animais , Bacillus/crescimento & desenvolvimento , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Fermentação , Glutationa Peroxidase/metabolismo , Humanos , Rim/lesões , Rim/microbiologia , Camundongos , Estresse Oxidativo/genética , Superóxido Dismutase/metabolismo , Ácido Úrico/sangue , Zearalenona/toxicidade
18.
Int J Surg ; 56: 320-327, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29969732

RESUMO

BACKGROUD: Inflammation can promote tumor growth, invasion, angiogenesis and even metastasis. Inflammatory markers have prognostic value in some malignancies. The aim of the present study was to examine whether neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) served as sensitive serum markers for predicting lymph node metastasis and prognostic factors in gastric cancer (GC) patients. METHODS: 904 consecutive patients who underwent radical total or subtotal gastrectomy between 2010 and 2011, were included in this study. The clinical utility of the NLR and PLR was evaluated by receiver operating characteristic (ROC) curves,Kaplan-Meier curves and Cox regression analyses were used to calculate the overall survival (OS) characteristics. RESULTS: We determined the cutoff values of NLR and PLR was 2.0 and 160 respectively according to the ROC curve. Both the NLR and PLR were significantly associated with LN (lymph node) metastasis, and high NLR and PLR groups were significantly associated with poor overall survival. Additionally, NLR and TNM stage were independent prognostic factors for overall survival, however, PLR had limited value. CONCLUSIONS: NLR and PLR levels may be valuable indexes for lymph node metastasis. Although both the PLR and NLR may have prognostic value of gastric cancer patients, NLR is better to predict overall survival than PLR.


Assuntos
Plaquetas , Metástase Linfática/diagnóstico , Linfócitos , Neutrófilos , Neoplasias Gástricas/sangue , Idoso , Biomarcadores Tumorais/sangue , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfonodos/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Valores de Referência , Análise de Regressão , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/secundário
19.
Int J Med Sci ; 15(5): 447-455, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29559833

RESUMO

Background: Keratinocytes are the predominant cell type in a cholesteatoma, and microRNA (miR)-203a has been shown to be essential for the growth and differentiation of keratinocytes. The regulatory mechanisms of miR-203a and Bmi1-the predicted target of miR-203a that is associated with cholesteatoma-have not been clarified. Methods: Real-time PCR and western blot were carried out for the detection of miRNAs, mRNAs, and proteins, including miR-203a, Bmi1, and phosphorylated (p-)Akt. Immunohistochemical staining was applied to observe the expression and distribution of Bmi1 and of p-Akt in cholesteatoma and in control retroauricular skin. The dual luciferase reporter assay was used to analyze the relationship between miR-203a and Bmi1. Ectopic miR-203a and Bmi1 were transfected into an immortalized line of human keratinocytes (HaCaT cells), and the roles of these molecules in cell proliferation, apoptosis, and migration were explored. Results: Cholesteatoma tissues were characterized by downregulation of miR-203a and concomitant upregulation of Bmi1. Results of the dual-luciferase reporter assay indicated that Bmi1 was a direct target gene of miR-203a. Silencing of miR-203a increased Bmi1 expression; promoted proliferation, colony formation, and migration of HaCaT cells; and inhibited apoptosis. Moreover, p-Akt was significantly increased in cholesteatoma tissues and was positively correlated with Bmi1. Suppression of Bmi1 reduced p-Akt expression in HaCaT cells; subsequent inhibition of miR-203a reversed this phenomenon. Conclusions: Our results reveal that miR-203a may regulate cholesteatoma growth and proliferation by targeting Bmi1. These findings provide insight for the development of novel nonsurgical options for cholesteatoma.


Assuntos
Proliferação de Células/genética , Colesteatoma/genética , MicroRNAs/genética , Complexo Repressor Polycomb 1/genética , Adolescente , Adulto , Idoso , Apoptose/genética , Linhagem Celular , Movimento Celular/genética , Criança , Colesteatoma/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética , Adulto Jovem
20.
Am J Transl Res ; 10(12): 4130-4140, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30662656

RESUMO

Radioresistance is an important obstacle to nasopharyngeal carcinoma (NPC) therapy. In this study, we explored the role of RNA-binding motif protein 3 (RBM3) in the radioresistance of NPC and its underlying mechanism. We measured the expression of RBM3 in 20 clinical NPC tissues and in NPC cell lines. We found that RBM3 was upregulated in radioresistant NPC tissues and cells. Radioresistant NPC cells (CNE1/IR) and parental NPC cells (CNE1) were subjected to RBM3-shRNA knockdown and RBM3 overexpression, respectively. RBM3 depletion in CNE1/IR cells sensitized cells to radiotherapy, increased DNA damage, and accelerated the rate of apoptosis. In contrast, RBM3 overexpression in CNE1 cells significantly enhanced radioresistance and reduced the rate of apoptosis. Additionally, radioresistance conferred by RBM3 was attributed to the activation of the AKT/Bcl-2 signaling pathway and reduction of caspase 3. Inhibition of AKT signaling attenuated RBM3-mediated radioresistance. Furthermore, RBM3 directly interacted with PI3K subunit p85 in NPC cell lines. Altogether, our data demonstrate that RBM3 enhances radioresistance by inhibiting the apoptotic response to radiotherapy through the PI3K/AKT/Bcl-2 signaling pathway. RBM3 may serve as a novel factor for predicting radioresistance and as a molecular target in the treatment of NPC.

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