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Long noncoding RNA MIR17HG was involved with the progression of non-small-cell lung cancer (NSCLC), but specific mechanisms of MIR17HG-mediated immune escape of NSCLC cells were still unknown. The present study investigated the function of MIR17HG on regulatory T cell (Treg)-mediated immune escape and the underlying mechanisms in NSCLC. Expression of MIR17HG and miR-17-5p in NSCLC tissue samples were detected using quantitative real-time PCR (qRT-PCR). A549 and H1299 cells were transfected with sh-MIR17HG, miR-17-5p inhibitor, or sh-MIR17HG + miR-17-5p inhibitor, followed by cocultured with Tregs. Cell proliferation was measured using 5-ethynyl-20-deoxyuridine (Edu) staining assay and cell counting kit-8 (CCK-8) assay. Flow cytometry was used for determining positive numbers of FOXP3+CD4+/CD25+/CD8+ Tregs. Through subcutaneous injection with transfected A549 cells, a xenograft nude mouse model was established. Weights and volumes of xenograft tumors were evaluated. Additionally, the expressions of immune-related factors including transforming growth factor beta (TGF-ß), vascular endothelial growth factor A (VEGF-A), interleukin-10 (IL-10), IL-4, and interferon-gamma (IFN-γ) in cultured cells, were evaluated by enzyme-linked immunosorbent assay and western blot analysis. Then, miR-17-5p was decreased and MIR17HG was enhanced in both NSCLC tissues and cell lines. MIR17HG knockdown significantly suppressed cell proliferation, tumorigenicity, and immune capacity of Tregs in A549 and H1299 cells, whereas sh-MIR17HG significantly reduced expression levels of VEGF-A, TGF-ß, IL-4, and IL-10 but promoted the IFN-γ level in vitro and in vivo. Moreover, downregulation of miR-17-5p significantly reversed the effects of sh-MIR17HG. Additionally, we identified that runt- related transcription factor 3 (RUNX3) was a target of miR-17-5p, and sh-MIR17HG and miR-17-5p mimics downregulated RUNX3 expression. In conclusion, downregulation of MIR17HG suppresses tumorigenicity and Treg-mediated immune escape in NSCLC through downregulating the miR-17-5p/RUNX3 axis, indicating that this axis contains potential biomarkers for NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Subunidad alfa 3 del Factor de Unión al Sitio Principal , Regulación hacia Abajo , Neoplasias Pulmonares , Ratones Desnudos , MicroARNs , ARN Largo no Codificante , Linfocitos T Reguladores , Animales , Humanos , Ratones , Células A549 , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 3 del Factor de Unión al Sitio Principal/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Ratones Endogámicos BALB C , MicroARNs/genética , ARN Largo no Codificante/genética , Linfocitos T Reguladores/inmunología , Escape del Tumor/genéticaRESUMEN
Propose: This meta-analysis aimed to determine whether 3D-printed artificial vertebral bodies (AVBs) have superior clinical efficacy compared to conventional titanium mesh cages (TMCs) for spinal reconstruction after total en bloc spondylectomy (TES) for spinal tumors. Methods: Electronic databases, including PubMed, OVID, ScienceDirect, Embase, CINAHL, Web of Science, Cochrane Library, WANFANG, and CNKI, were searched to identify clinical trials investigating 3D-printed AVB versus conventional TMC from inception to August 2023. Data on the operation time, intraoperative blood loss, preoperative and postoperative visual analogue scale (VAS) scores, preoperative and postoperative Frankel classification of spinal cord injury, vertebral body subsidence, and early complications were collected from eligible studies for a meta-analysis. Data were analyzed using Review Manager 5.4 and Stata 14.0. Results: Nine studies assessing 374 patients were included. The results revealed significant differences between the 3D-printed AVB and conventional TMC groups with regard to operation time (P = 0.04), intraoperative blood loss (P = 0.004), postoperative VAS score (P = 0.02), vertebral body subsidence (P < 0.0001), and early complications (P = 0.02). Conversely, the remaining preoperative VAS score and Frankel classifications (pre-and postoperative) did not differ significantly between the groups. Conclusion: The 3D-printed AVB in spinal reconstruction after TES for spinal tumors has the advantages of a short operative time, little intraoperative blood loss, weak postoperative pain, low occurrence of vertebral body subsidence and early complications, and a significant curative effect. This could provide a strong basis for physicians to make clinical decisions. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023441521, identifier CRD42023441521.
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BACKGROUND: It is commonly accepted that surgical treatment is an essential component of the comprehensive management of metastatic spinal malignancies. However, up until now, the clinical classification of metastatic spinal malignancies has not been well-structured. METHODS: After IRB approval, 86 patients with metastatic spinal malignancies were adopted. According to the vascular distribution, stability of vertebrae, and degree of nerve compression, metastatic spinal malignancies can be classified into five types. Tumors classified as type I typically appear in the vertebral body. Type II tumors are those that develop in the transverse processes, superior and inferior articular processes, and spinal pedicles. Type III denotes malignancies that are present in the spinous process and vertebral plate. Types IVa and IVb are included in type IV. Type IVa combines type I and type II, whereas type IVb combines type II and type III. Type V tumors are those of types I, II, and III that co-occur and spread in different directions into the spinal canal. 20 of included 86 patients who did not receive segmental arterial embolization were set as the non-embolization group. The embolization group included 24 patients who received segmental arterial embolization on both sides of the diseased vertebrae. 42 patients were included in the offending embolization group after receiving responsible arterial embolization. A surgical intervention was performed within 24 h following an embolization. Surgical intervention with the purpose of removing as much of the tumor as possible and providing an effective reconstruction of the spinal column. RESULTS: In comparison with the non-embolization group and embolization group, the offending embolization group presented unique advantages in terms of bleeding volume (p<0.001), operation time (p<0.001), and local recurrence rate within 12 months (p=0.006). CONCLUSION: By significantly reducing surgical trauma and local recurrence rate (12 months), responsible arterial vascular embolization procedures together with associated surgical protocols developed on the basis of the clinical classification of metastatic spinal malignancies, are worthy of clinical dissemination.
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Neoplasias de la Columna Vertebral , Humanos , Estudios Retrospectivos , Estudios de Casos y Controles , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/patología , Columna Vertebral/patología , Canal Medular , Resultado del TratamientoRESUMEN
BACKGROUND: Autogenous granular bone graft (AG), autogenous massive bone graft (AM), and titanium mesh bone graft (TM) are the three commonly utilized bone implant methods for spinal tuberculosis. However, the gold standard is still controversial. Therefore, this study aimed to compare the clinical efficacy and surgical safety of three primary bone graft modalities. METHODS: For systematic literature review, several databases, including PubMed, Embase, and Web of Science, were searched up to December 2022. Stata (version 14.0) was employed for data analysis. RESULTS: Our network meta-analysis included 517 patients from 7 articles whose qualities are acceptable based on our quality assessment criteria. In direct comparison, AG was associated with a shorter operation time (MD = 73.51; CI 30.65-116.37) and a lesser blood loss (MD = 214.30; CI 7.17-421.44) than AM. TM had fewer loss of Cobb angle than AG (MD = 1.45; CI 0.13-2.76) and AM (MD = 1.21; CI 0.42-1.99). Compared with AG, TM (MD = 0.96; CI 0.06-1.87) was related to a shorter bone graft fusion time. In indirect comparison, for the clinical parameters, the rank of CRP (from best to worst) was as follows: TM (58%) > AM (27%) > AG (15%), the rank of ESR (from best to worst) was as follows: AG (61%) > AM (21%) > TM (18%), and the rank of VAS (from best to worst) was as follows: AG (65%) > TM (33%) > AM (2%). In the aspect of surgical data, what is noteworthy is that AG showed less blood loss [AG (93%) > TM (6%) > AM (1%)], operative time [AG (97%) > TM (3%) > AM (0)], and complications [AG (75%) > TM (21%) > AM (4%)] than AM and TM. As for imaging parameters, the rank of the loss of Cobb angle (from best to worst) was as follows: TM (99%) > AM (1%) > AG (0). Moreover, TM showed a shorter bone graft fusion time than AM and AG: TM (96%) > AM (3%) > AG (1%). CONCLUSIONS: The results indicated that AG might be the optional treatment for spinal tuberculosis owing to the outcomes of surgical safety. Moreover, TM is another right choice which can significantly reduce the loss of Cobb angle and shorten bone graft fusion time with long-term follow-up.
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Fusión Vertebral , Tuberculosis de la Columna Vertebral , Humanos , Tuberculosis de la Columna Vertebral/diagnóstico por imagen , Tuberculosis de la Columna Vertebral/cirugía , Metaanálisis en Red , Fusión Vertebral/efectos adversos , Fusión Vertebral/métodos , Vértebras Lumbares/cirugía , Vértebras Torácicas/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVE: Total en bloc spondylectomy (TES) is an important surgical treatment for spinal tumors that can achieve en bloc resection of the affected vertebral body by using the T-saw. However, the conventional TES process and the surgical instruments currently in use have some inconveniences, which may lead to longer operative times and a higher incidence of complications. To address these obstacles, we developed a modified TES technique using a homemade intervertebral hook blade. The objectives of this study were to describe our modified total en bloc spondylectomy (TES) using a homemade intervertebral hook blade and to assess its clinical effects in patients with spinal tumors. METHODS: Twenty-three consecutive patients with spinal tumors were included from September 2018 to November 2021. Eleven patients underwent a modified TES using an intervertebral hook blade, and 12 patients underwent a conventional TES using a wire saw. Details of the modified technique for TES were depicted, and the intraoperative blood loss, operative time, and improvement in pain symptom and neurological function measured by visual analog score (VAS) and American Spinal Injury Association (ASIA) score of all patients was reviewed and analyzed. Nonparametric analysis of covariates (ANCOVA) was performed to compare the clinical outcomes between patients treated with modified TES and conventional TES. RESULTS: The modified TES significantly reduced operative time (F = 7.935, p = 0.010) and achieved favorable improvement of neurological function (F = 0.570, p = 0.459) and relief of pain (F = 3.196, p = 0.088) compared with the conventional TES group. The mean intraoperative blood loss in the modified TES group (2381.82 ml) was lower than that in the conventional TES group (3558.33 ml), although the difference was not statistically significant (F = 0.677, p = 0.420). CONCLUSIONS: Modified TES using the intervertebral hook blade can effectively reduce the operation time and intraoperative bleeding, and meanwhile ensure the improvement of neurological function and relief of pain symptoms, suggesting that this modified technique is feasible, safe, and effective for spinal tumors.
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Neoplasias de la Médula Espinal , Neoplasias de la Columna Vertebral , Humanos , Neoplasias de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/patología , Estudios Retrospectivos , Pérdida de Sangre Quirúrgica , Dolor , Instrumentos QuirúrgicosRESUMEN
With the development of material science, additive manufacturing technology has been employed for pelvic surgery, addressing the challenges, such as the complex structure of the pelvis, difficulty in exposing the operative area, and poor visibility, of the traditional pelvic surgery. However, only limited studies have been done to review the research hotspots and trends of the additive manufacturing technology applied for pelvic surgery. In this study, we comprehensively analyzed the literatures related to additive manufacturing technology in pelvic surgery by a bibliometrics analysis and found that additive manufacturing technology is widely used in several aspects of preoperative diagnosis, preoperative planning, intraoperative navigation, and personalized implants for pelvic surgery. Firstly, we searched and screened 856 publications from the Web of Science Core Collection (WoSCC) with TS = (3D printing OR 3D printed OR three-dimensional printing OR additive manufacturing OR rapid prototyping) AND TS = (pelvis OR sacrum OR ilium OR pubis OR ischium OR ischia OR acetabulum OR hip) as the search strategy. Then, 565 of these were eliminated by evaluating the titles and abstracts, leaving 291 pieces of research literature whose relevant information was visually displayed using VOSviewer. Furthermore, 10 publications with high citations were selected by reading all publications extensively for carefully evaluating their Titles, Purposes, Results, Limitations, Journal of affiliation, and Citations. Our results of bibliometric analysis demonstrated that additive manufacturing technology is increasingly applied in pelvic surgery, providing readers with a valuable reference for fully comprehending the research hotspots and trends in the application of additive manufacturing technology in pelvic surgery.
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BACKGROUND: In recent years, researchers have proposed a number of adjuvant methods for extended curettage of giant cell tumors of the bone. However, various schemes have significant differences in efficacy and safety. Therefore, this article will describe an empirical expanded curettage protocol, 'triple clear', in detail to show the effect of the efficient surgical protocol. METHOD: Patients with Campanacci grades II and III primary GCTB who were treated with either SR (n = 39) or TC (n = 41) were included. Various perioperative clinical indicators, including the therapy modality, operation time, Campanacci grade, and filling material were recorded and compared. The pain level was determined by the visual analog scale. Limb function was determined by the Musculoskeletal Tumour Society (MSTS) score. Follow-up time, recurrence rates, reoperation rates, and complication rates were also recorded and compared. RESULT: The operation time was 135.7 ± 38.4 min in the TC group and 174.2 ± 43.0 min in the SR group (P < 0.05). The recurrence rates were 7.3% in the TC group and 8.3% in the SR group (P = 0.37). The MSTS scores at three months after surgery were 19.8 ± 1.5 in the TC group and 18.8 ± 1.3 in the SR group. The MSTS scores at two years were 26.2 ± 1.2 in the TC group and 24.3 ± 1.4 in the SR group (P < 0.05). CONCLUSION: TC is recommended for patients with Campanacci grade II-III GCTB and for those with a pathological fracture or slight joint invasion. Bone grafts may be more suitable than bone cement in the long term.
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Neoplasias Óseas , Fracturas Espontáneas , Tumor Óseo de Células Gigantes , Humanos , Neoplasias Óseas/patología , Fracturas Espontáneas/etiología , Fracturas Espontáneas/cirugía , Tumor Óseo de Células Gigantes/patología , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/complicaciones , Células Gigantes/patología , Estudios Retrospectivos , Legrado , Resultado del TratamientoRESUMEN
Purpose: To examine the effects of 3D printing model in total en bloc spondylectomy (TES). Methods: We performed a retrospective chart review of 41 cases of spinal tumors at our institution between 2017 and 2020, in which TES was applied. There were 19 cases with 3D printing model and 22 cases without 3D printing model. Operation time, intraoperative blood loss, excision range, complications, VAS, and ASIA grades were recorded. Statistical methods were used to analyze the data. KaplanMeier survival curve was made to evaluate the survival. Result: There were significant differences in intraoperative blood loss between the two groups. The rate of R0 resection and tumor envelope preservation were higher in 3D group than that in non-3D group. In 3D group, the complications included surgical site infection (5.2%) and cerebrospinal fluid leak (15.7%). In non-3D group, the complications included cerebrospinal fluid leak (27.3%) and nerve root injury (13.6%). The pain and neurological dysfunction were significantly relieved before and after surgery in 3D group. However, the neurological relief in non-3D group patients was not complete. The VAS scores of non-3D group at 6 months after surgery were much higher than that of 3D group. Conclusion: The application of 3D printing model not only helps surgeons observe the morphology, invasion range, and anatomic relationship of the tumor preoperatively, but also assists surgeons to judge, locate, and separate the tumor intraoperatively. For spinal malignancies, the 3D printing model is worth promoting.
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Neoplasias de la Columna Vertebral , Pérdida de Sangre Quirúrgica , Pérdida de Líquido Cefalorraquídeo , Humanos , Impresión Tridimensional , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/cirugíaRESUMEN
OBJECTIVES: The newly released eighth edition of the American Joint Committee on Cancer TNM staging system for lung cancer seeks to improve prognostic accuracy but lacks external validation for small cell lung cancer (SCLC). Moreover, previous studies posed a few questions concerning survival differences for patients with specific site N3 node involvement or single-site metastasis (SSM) in different distant organs. The aim of this study was to validate the eighth edition of the TNM classification for SCLC in an independent multi-institutional cohort from China and answer the questions raised by the previous research. METHODS: Patients with SCLC from four Chinese cancer centers between 2009 and 2019 were reclassified according to the seventh and eighth edition of the TNM classification. Survival was estimated using the Kaplan-Meier method. Comparisons between adjacent categories and stage groups were performed using Cox proportional hazard regression. R2 statistics were calculated to evaluate the discriminating performance of editions. RESULTS: Of 3384 enrolled cases, 3358 had clinical stage, 537 had pathological stage, and 511 had both. Progressive deterioration of survival was observed with advancing of TNM categories and stages both in the seventh and the eighth edition. The eighth edition stages had a higher R2 statistic than the seventh edition (0.207 versus 0.197). Newly defined categories M1b and M1c and stages IIIC, IVA and IVB in the eighth edition discriminated groups with significantly different prognosis. Patients with N3 contralateral supraclavicular nodes had a significantly worse prognosis than those without (p = 0.032). For patients with single-site metastasis, liver involvement showed a worse prognosis compared to brain involvement (p = 0.030). CONCLUSIONS: Our study provided an external validation of the eighth edition of the TNM classification for lung cancer in Chinese patients with SCLC, and confirmed its improved prognostic accuracy compared with the seventh edition. Patients with N3 and M1b might represent heterogeneous populations that warrant further research.
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Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Estudios de Cohortes , Humanos , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/patologíaRESUMEN
The relationship between pore architecture and structure performance needs to be explored, as well as confirm the optimized porous structure. Because of the linear correlation between constant C and pore architecture, triply periodic minimal surface (TPMS) based porous structures could be a controllable model for the investigation of the optimized porous structure. In the present work, three types of TPMS porous scaffolds (S, D and G) combined with four constants (0.0, 0.2, 0.4 and 0.6) were designed, and built successfully via the selective laser melting (SLM) technology. The designed feature and mechanical property of porous scaffolds were investigated through mathematical method and compression test. And the manufactured samples were co-cultured with rMSCs for the compatibility study. The results indicated that the whole manufacturing procedure was good in controllability, repeatability, and accuracy. The linear correlation between the porosity of TPMS porous scaffolds and the constant C in equations was established. The different TPMS porous scaffolds possess the disparate feature in structure, mechanical property and cell compatibility. Comprehensive consideration of the structure features, mechanical property and biology performance, different TPMS structures should be applied in appropriate field. The results could guide the feasibility of apply the different TPMS architectures into the different part of orthopedic implants.
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Objective: To explore the clinical value of specific miRNA in patients with acute promyelocytic leukemia. Methods: 129 patients with acute promyelocytic leukemia diagnosed in our hospital from January 2015 to January 2020 were selected as the observation group. At the same time, 74 patients with nonacute promyelocytic leukemia who underwent bone marrow aspiration were included as the control group. The expression levels of miR-126-5p and miR-13, different characteristic parameters, and prognosis were compared between the two groups, and the clinical significance of miR-126-5p and miR-13 in acute promyelocytic leukemia was analyzed. Results: The expression of miR-126-5p (12.31 ± 2.25 versus 17.30 ± 3.28) and miR-13 (16.05 ± 3.47 versus 21.66 ± 2.18) in the observation group was significantly lower than that in the control group (P < 0.05). The expression level of miR-126-5p was significantly correlated with lactate dehydrogenase level, HGB level, NPM1 mutant type, and complete remission (P < 0.05). The expression level of miR-13 was significantly correlated with HGB level, NPM1 mutant type, and complete remission (P < 0.05). Both expression levels of miR-126-5p and miR-13 were not correlated with sex, age, WBC, PLT, proportion of bone marrow primordial cells, hepatomegaly, splenomegaly, lymph node enlargement, and FLT3-ITD (P > 0.05). Cox multivariate regression analysis showed that peripheral blood WBC, bone marrow blast cell count, and miR-126-5p and miR-13 were prognostic factors in patients with acute promyelocytic leukemia (P < 0.05). The sensitivity, specificity, accuracy, and AUC of serum miR-126-5p prediction were 75.83%, 84.56%, 82.17%, and 0.729, respectively. The sensitivity, specificity, accuracy, and AUC of serum miR-13 prediction were 78.64%, 88.49%, 86.20% and 0.882, respectively. Conclusion: Serum miR-126-5p and miR-13 are closely related to the prognosis of patients with acute promyelocytic leukemia. Serum miR-126-5p and miR-13 can be used as reliable indexes to predict the prognosis of patients.
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MicroRNA-200c (miR-200c) generally acts as a tumor suppressor in multiple cancer types and a promising therapeutic target in tumorigenesis. However, only a few studies have explained the role of miR-200c in the development of osteosarcoma (OS). In this study, we investigated the role of miR-200c in OS progression and identified the regulatory pathway protein NDN involved in inhibiting the occurrence and development of OS. Firstly, we found that miR-200c is downregulated in OS cells and tissues. As well, in vitro and in vivo experiments showed that upregulating miR-200c inhibits the proliferation, invasion, metastasis of Saos-2 cells, promotes the apoptosis of Saos-2 cells and suppresses tumor growth in mice, indicating miR-200c plays a major role in regulating the OS progression. Furthermore, bioinformatics analysis showed that an anti-tumor protein, necdin (NDN), might be a potential target by miR-200c. To verify this hypothesis, we measured the expression level of NDN in OS cells and tissues and found NDN is downregulated, suggesting NDN is functional in OS progression. Moreover, we found that the expression levels of NDN and miR-200c in in vivo and in vitro experiments were positively correlated. However, the results of dual-luciferase reporter gene experiment showed miR-200c does not directly act on the 3' untranslated region (UTR) of NDN gene, indicating that NDN might be an important pathway protein which regulates OS progression in the presence of miR-200c. Therefore, miR-200c/NDN could be potential targets for developing effective treatment against OS.
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Neoplasias Óseas , MicroARNs , Proteínas del Tejido Nervioso , Proteínas Nucleares , Osteosarcoma , Regiones no Traducidas 3'/genética , Animales , Neoplasias Óseas/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Ratones , MicroARNs/genética , Proteínas del Tejido Nervioso/genética , Proteínas Nucleares/genética , Osteosarcoma/genéticaRESUMEN
We analyzed the treatment effects of chidamide and decitabine in combination with a HAG (homoharringtonine, cytarabine, G-CSF) priming regimen (CDHAG) in acute myeloid leukemia (AML) patients with TP53 mutation. Seven TP53 mutated AML patients were treated with CDHAG. The treatment effects were assessed using hemogram detection and bone marrow aspirate. The possible side effects were evaluated based on both hematological and non-hematological toxicity. Four of the seven patients were classified as having achieved complete remission after CDHAG treatment; one patient was considered to have achieved partial remission, and the remaining two patients were considered in non-remission. The overall response rate (ORR) to CDHAG was 71.4%. Regarding the side effects, the hematological toxicity level of the seven patients ranged from level III to level IV, and infections that occurred at lung, blood, and skin were recorded. Nausea, vomiting, liver injury, and kidney injury were also detected. However, all side effects were attenuated by proper management. The CDHAG regimen clearly improved the ORR (71.4%) of TP53-mutated AML patients, with no severe side effects.
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Aminopiridinas/uso terapéutico , Antimetabolitos Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Decitabina/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Proteína p53 Supresora de Tumor , Adulto , Anciano , Citarabina/uso terapéutico , Femenino , Factor Estimulante de Colonias de Granulocitos , Homoharringtonina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Mutación , Inducción de Remisión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Silencing of the periostin gene (POSTN) can inhibit the biological process of several different cancers, and this inhibition may be related to down-regulation of PI3K/AKT signaling. However, the effect of POSTN on the progression, proliferation, and invasion of osteosarcoma (OS) remain unclear. METHODS: We used the Gene Expression Omnibus (GEO) database to screen datasets on in situ OS and lung metastases to identify core genes and potential pathways. We used additional bioinformatics tools to identify protein-protein interactions (PPIs) and gene networks, and selected the top seven genes whose expression had the strongest correlations with other genes. RESULTS: The results indicated that POSTN was a major hub gene. Subsequent analysis of gene expression profiles showed that POSTN was highly expressed in 262 cases with sarcoma and expression was closely related to poor prognosis. We also performed enrichment analysis to identify differentially expressed genes and used real-time PCR, western blotting, and immunohistochemistry analyses to measure POSTN expression in cells and tissues. Transfection of a POSTN-shRNA plasmid into cultured OS cells (Saos-2) effectively inhibited the proliferation, invasion, and migration of these cells. Taken together, our results suggest that POSTN may play a role in promoting the proliferation and metastasis of OS by activation of the PI3K/Akt signaling pathway. CONCLUSIONS: Our results provide a preliminary characterization of the mechanism by which POSTN may regulate the migration and invasion of OS cells and also provide a theoretical basis for identifying biomarkers that have potential use for the diagnosis and treatment of OS.
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The coupling and coordination relationship between ecology and the economy in the Yellow River Basin is a hot topic in sustainable development research. Said research has important guiding significance for the ecological security and comprehensive development of the Yellow River Basin. Taking the Yellow River Basin as the object of our study, based on the data of the economy, energy consumption data, ecology data and water resources data, we construct an indicator system of the economic development and ecological status of the Yellow River Basin and use the principal component analysis method to calculate the economic development and ecological status index. Then, we use the evaluation method, the coupling degree model and the coupling coordination degree model to analyze the time and space evolution trends of economic development and ecological state, coupling degree and coupling coordination degree. The results show that: (1) From 2000 to 2018, the economic development index of the Yellow River Basin rose steadily; the ecological status index showed a slow rise and then a downward trend. (2) The degree of coupling between economic development and ecological state has been considered as intensity coupling after 2005. The coupling trend slowly increased and then decreased, indicating that the interaction effect between the economy and ecology was first significantly enhanced and then slowly weakened. (3) The degree of coupling coordination increased from 0.2994 to 0.6266 and then decreased to 0.5917, reflecting the continuous improvement of the relationship between the regional economy and the ecological environment and the trend toward coordination. From 2015 to 2018, due to the gradual increase in the difference between economic development and ecological conditions, the coupling and coordination between the two decreased. Studies have shown that ecological construction and protection should be strengthened to ease the contradiction between the economy and ecology and achieve coordinated development.
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Desarrollo Económico , Ríos , China , Conservación de los Recursos Naturales , Ecosistema , Desarrollo Sostenible , Recursos HídricosRESUMEN
The ecological system is the basis of human survival and global environmental protection. In the process of development, countries will pay close attention to the changing state of the ecosystem. Taking the ecosystem pattern as the research object, a three-layer analysis method was proposed. The transfer matrix and landscape index were used as the first layer to analyze the basic changes. Grey correlation, range-coupling coordination and relative priority were used as the second layer to analyze the reasons of the change. The interval-entropy weight, TOPSIS (Technique for Order Preference by Similarity to an Ideal Solution), was used as the third layer to evaluate the quality of the change. The ten counties in the worst-hit areas of the Wenchuan earthquake were analyzed from different angles, with county region, intensity zone and ecosystem as the objects, and the following results were obtained: (1) Taking Mianzhu City as an example, from 2000 to 2010 and 2018, the conversion ratio of forest, grassland and farmland is 54.24, 59.19, 17.21, 20.06, 37.39 and 52.86%, which were distributed in the north, central and southern parts, respectively. (2) Taking the ninth intensity zone as an example, the forest landscape fragmentation increased, disturbance decreased, and species diversity increased. There is a high influence and restriction relationship between ecosystem and landscape pattern in the total landscape area change. Additionally, the relationship between them tends to develop in a benign way. As of 2018, it is in the change state of moderate imbalance-ecosystem lag. (3) Taking the county ecosystem change as an example, urban type is the best in the counties of ecosystem change, of which Shifang is the best and Pingwu is the worst. The results show that this method can effectively compare and analyze the changes in the multi-regional ecosystem pattern, which has the characteristics of universality and can also be applied to the research of ecosystem pattern change in special regions.
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Desastres , Terremotos , China , Ciudades , Conservación de los Recursos Naturales , Ecosistema , HumanosRESUMEN
RATIONALE: Some acute myeloid leukemia (AML) patients are unresponsive to treatment or have remission followed by worsening of disease (known as relapsed/refractory AML [R/RAML]) after standardized treatment. The CAG/HAG regimen is not often used clinically because heterogenous patient responses, resistance, and hematopoietic bone marrow dysfunction have been reported with its use. We present 2 cases of R/RAML treated with a new combined therapy (venetoclax+ hypomethylating agents [HMAs]) in which the HAG dose was adjusted and effective in the first course of treatment. PATIENT CHARACTERISTICS: Case 1 involved a 23-year-old man who had suffered from AML for >4 years, and his FLT3 mutation status was positive at the initial diagnosis. After the first course of treatment with the standard-dose "Da" plan, the patient experienced complete remission. During the subsequent courses of treatment, the patient experienced 6 recurrences and was treated with the "ID Ara-C + MIT + sidaaniline" and "CAG + sidaaniline" regimens. However, the disease did not respond. Case 2 involved a 26-year-old man who received chemotherapy with the "Da," "ID Ara-C," "decitabine + half-dose CAG," and "HAE" regimens. In this patients, remission could not be achieved. Reintroduction of the "ia" scheme also failed after treatment in our hospital. DIAGNOSIS: Two patients were diagnosed with R/RAML. INTERVENTIONS: The patient in case 2 received chemotherapy interventions, whereas the patient in case 1 refused to receive medical services at our hospital. OUTCOMES: The patient in case 1 was discharged after complete response treatment due to economic reasons and relapsed 2 months later. The patient ultimately died of infection and heart failure. The patient in case 2 is receiving a second cycle of chemotherapy. LESSONS: We recommend the "venetoclax + HMAs combined with dose-adjusted CAH/HAG" regimen as an effective treatment for adult R/RAML.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Azacitidina/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Citarabina/administración & dosificación , Decitabina/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Homoharringtonina/administración & dosificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Sulfonamidas/administración & dosificación , Adulto , Combinación de Medicamentos , Resultado Fatal , Humanos , Masculino , Adulto JovenRESUMEN
OBJECTIVE: To investigate the clinical features, accompanying gene mutation characteristics and prognostic factors of adult patients with acute myeloid leukemia with mutated NPM1 (NPM1+AML). METHODS: Seventy-three patients with newly diagnosed adult NPM1+AML were selected. The mutations of 22 genes were detected by second generation sequencing and 43 fusion genes of AML were detected by real-time fluorescent quantitative PCR. The Kaplan-Meier survival curve and Cox multivariate regression analysis were used to study the prognostic factors. RESULTS: A total of 74 NPM1 site mutations were detected in 73 patients with NPM1+AML. The incidence rates were 92.0% L287fs, 2.7% Q289fs and W288fs, 1.4% L258fs and Q289H, among which 1 patient had 2 NPM1 mutations; the different mutation sites had no effect on the prognosis of NPM1+AML. The median value of NPM1 variant allele frequency (VAF) was 35.4% (1.8%-56.6%). Based on the uppermost quartile of 38.4%, the patients were classified as NPM1 VAF>38.4% (NPM1highAML) and NPM1 VAF≤38.4% (NPM1lowAML). Compared with NPM1lowAML, the early mortality rate was statistically significantly higher (33.3% vs 7.3%, P<0.05), and median EFS (148 dï¼95%CI 58-238 d vs 372 dï¼95%CI 264-480 d) (P<0.01) and median OS (179 d 95%CI 6-352 d vs 444 d) (P<0.01) were significantly shorter in NPM1high AML. A total of 126 accompanying gene mutation sites were detected in 87.7% of patients with NPM1+AML. The patients with NRAS gene mutation displayed a higher rate of complete remission (100% vs 58%) (P<0.05) and longer median OS (not reached to 320 d, 95%CI 150-490 d) (P<0.05). The 43 fusion genes were examined in 65 out of 73 cases of NPM1+AML, and in all the patients the fusion gene test was negative. Multivariate analysis showed that NPM1 VAF>38.4% was an independent prognostic factor for EFS (HR=3.1, 95% CI 1.6-6.4, P<0.01) and OS (HR=3.0, 95% CI 1.4-6.2, P<0.01). CONCLUSION: The NPM1 gene mutation in AML patients often is accompanied by other gene mutations, while the coexistence of fusion genes is rare; high NPM1 mutant allele burden is an independent prognostic factor for adult AML patients with mutated NPM1.
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Leucemia Mieloide Aguda , Proteínas Nucleares/genética , Alelos , Humanos , Leucemia Mieloide Aguda/genética , Mutación , Nucleofosmina , Pronóstico , Tirosina Quinasa 3 Similar a fmsRESUMEN
In the title compound, C(37)H(40)N(4)O(2), the xanthene and spiro-lactam rings are almost planar, with r.m.s. deviations from the mean planes of 0.223â (2) and 0.057â (2)â Å, respectively, and form a dihedral angle of 85.76â (3)°. The dihedral angle between the xanthene mean plane and the benzene ring is 87.16â (5)°. One of the two ethyl groups of one of the diethyl-amino groups is disordered over two sets of sites [0.76â (1):0.24â (1)].