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Based on the coherence theory for non-stationary optical fields, we introduce a new class of partially coherent pulse sources with multi-cosine-Gaussian correlated Schell-model (MCGCSM) and derive the analytic expression for the temporally mutual coherence function (TMCF) of an MCGCSM pulse beam when it propagates through dispersive media. The temporally average intensity (TAI) and the temporal degree of coherence (TDOC) of the MCGCSM pulse beams spreading in dispersive media are investigated numerically, respectively. Our results show that over propagation distance, the evolution of pulse beams is from the primary single beam into multiple subpulses or form flat-topped TAI distributions by controlling source parameters. Moreover, when the chirp coefficient s < 0, the MCGCSM pulse beams through dispersive media will show the characteristics of two self-focusing processes. The reason why there are two self-focusing processes is explained from the perspective of physical meaning. The results in this paper can open the applications of pulse beams in multiple pulse shaping and laser micromachining and material processing.
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Noise-induced hearing loss (NIHL) seriously affects the life quality of humans and causes huge economic losses to society. To identify novel genetic loci involved in NIHL, we conducted a genome-wide association study (GWAS) for this symptom in Chinese populations. GWAS scan was performed in 89 NIHL subjects (cases) and 209 subjects with normal hearing who have been exposed to a similar noise environment (controls), followed by a replication study consisting of 53 cases and 360 controls. We identified that four candidate pathways were nominally significantly associated with NIHL, including the Erbb, Wnt, hedgehog and intraflagellar transport pathways. In addition, two novel index single-nucleotide polymorphisms, rs35075890 in the intron of AUTS2 gene at 7q11.22 (combined P = 1.3 × 10-6 ) and rs10081191 in the intron of PTPRN2 gene at 7q36.3 (combined P = 2.1 × 10-6 ), were significantly associated with NIHL. Furthermore, the expression quantitative trait loci analyses revealed that in brain tissues, the genotypes of rs35075890 are significantly associated with the expression levels of AUTS2, and the genotypes of rs10081191 are significantly associated with the expressions of PTPRN2 and WDR60. In conclusion, our findings highlight two novel loci at 7q11.22 and 7q36.3 conferring susceptibility to NIHL.
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Estudio de Asociación del Genoma Completo/métodos , Pérdida Auditiva Provocada por Ruido/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas Adaptadoras Transductoras de Señales/genética , China , Proteínas del Citoesqueleto/genética , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Proteínas Tirosina Fosfatasas Clase 8 Similares a Receptores/genética , Factores de Transcripción/genéticaRESUMEN
DNA methylation markers in the peripheral blood are able to be applied to treat epithelial cancer. Nevertheless, the diagnostic potential value of it for ovarian cancer (OV) has not been studied. The study aimed to explore the difference of DNA methylation in peripheral blood between OV patients and healthy women. Firstly, the whole blood of DNA methylation data was provided by the Gene Expression Omnibus (GEO) database. The linear model was applied to the identification of significantly differentially expressed methylated CpG sites (differentially methylation sites [DMP]), and the further screen of co-expression CpG sites (Co-DMP). A total of 2812 DMPs were identified, and weighted gene co-expression network analysis helped to obtain seven co-expression modules. Among them, the yellow module was the most related to OV. Co-DMPs (167) in the yellow module were mainly distributed near the transcription start sites. However, most of them were not in the CpG island. Least absolute shrinkage and selection operator (LASSO) regression analysis was applied to the identification of stable OV-related blood biomarkers that six Co-DMPs (cg00134539, cg00226923, cg25268718, cg25697314, cg25839227, cg26574610) with the highest frequency were found as potential biomarkers. Finally, the diagnostic classifier was established using the support vector machine (SVM) with the accuracy rate of 87.1% and 74.5% in training data set and validation data set, respectively. To sum up, a new feature was provided here for the diagnosis of OV, which is helpful for the diagnosis and individualized treatments of early OV.
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Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Islas de CpG , Metilación de ADN , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Ováricas/diagnóstico , Estudios de Casos y Controles , Femenino , Humanos , Neoplasias Ováricas/sangre , Neoplasias Ováricas/genética , PronósticoRESUMEN
BACKGROUND: Ovarian cancer (OC) is the gynecologic cancer with the highest mortality. Circular RNAs (circRNAs) play a vital role in the development and progression of cancer. This study aimed to explore the potential role of circ_0015756 in OC and its molecular mechanism. METHODS: The levels of circ_0015756, microRNA-942-5p (miR-942-5p) and Cullin 4B (CUL4B) were determined by quantitative real-time PCR (qRT-PCR) or Western blot assay. Cell proliferation, apoptosis, migration and invasion were assessed by Cell Counting Kit-8 (CCK-8), colony formation assay, flow cytometry and transwell assay. The levels of proliferation-related and metastasis-related proteins were measured by Western blot assay. The relationship between miR-942-5p and circ_0015756 or CUL4B was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Xenograft assay was used to analyze tumor growth in vivo. RESULTS: Circ_0015756 and CUL4B levels were increased, while miR-942-5p level was decreased in OC tissues and cells. Depletion of circ_0015756 suppressed proliferation, migration and invasion and promoted apoptosis in OC cells. Down-regulation of circ_0015756 hindered OC cell progression via modulating miR-942-5p. Also, up-regulation of miR-942-5p impeded OC cell development by targeting CUL4B. Mechanistically, circ_0015756 up-regulated CUL4B via sponging miR-942-5p. Moreover, circ_0015756 silencing inhibited tumor growth in vivo. CONCLUSION: Knockdown of circ_0015756 suppressed OC progression via regulating miR-942-5p/CUL4B axis, suggesting that circ_0015756 might be a potential therapeutic target for ovarian cancer.
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We establish the propagation model of orbital angular momentum (OAM) modes carried by hollow vortex Gaussian (hvG) beams propagating in anisotropic atmospheric turbulence. Effects of light source parameters and atmospheric conditions on the OAM mode propagation performance are investigated in detail. The findings indicate the hvG beam with a smaller OAM quantum number, a larger beam order, or a longer source wavelength has more robust resistance to atmospheric turbulence interference. The waist width of the light source has different influences on the OAM mode propagation at different propagation distances. Atmospheric turbulences with larger values of anisotropy, inner-scale factor, non-Kolmogorov power spectrum index, and altitude are favorable for the OAM mode propagation. These research results are conducive to optimizing the design of light sources and space wireless communication systems with hvG beams.
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The propagation model of orbital angular momentum (OAM) modes carried by the perfect vortex (pv) beam through anisotropic oceanic turbulence links is established and the factors influencing the OAM propagation are discussed. The findings show that the self-focusing property of pv beams is beneficial to the propagation of OAM modes: a smaller topological charge, a smaller initial radius, and an optimized half-ring width can alleviate degrading effects of turbulence on the pv beam. Additionally, the pv beam with a longer wavelength is more resistant to turbulent interference. The oceanic conditions with a higher dissipation rate of kinetic energy per unit mass of seawater, larger values of anisotropy and inner-scale factor, a smaller temperature-salinity contribution ratio, or a lower mean-squared temperature dissipation rate can improve the signal mode detection probability. The results are expected to further optimize the design of OAM-based underwater wireless communication systems.
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BACKGROUND: In vitro hemolysis is still the most common source of pre-analytical nonconformities. This study aimed to investigate the hemolytic effects on commonly used biochemical tests as well as to determine the hemolysis index (HI) thresholds on Siemens Advia 2400 chemistry analyzer. METHODS: Peripheral blood samples were collected from forty healthy volunteers. Hemolysis was achieved using syringes. Five hemolysis levels were produced including the no hemolysis group, slight hemolysis group, mild hemolysis group, moderate hemolysis group, and heavy hemolysis group. We then used the bias from baseline (no hemolysis) and HI to construct regression functions. The HI corresponding to the bias limits was considered as HI thresholds. We chose the total allowable error (TAE) as the bias limit. RESULTS: Of the twenty-eight analytes, ten analytes had clinical significance. Creatine kinase-MB, creatine kinase, potassium, aspartate aminotransferase, and hydroxybutyrate dehydrogenase were all positively affected; the corresponding HI threshold was 45.2, 99.96, 4.07, 10.16, and 7.94, respectively. Lactate dehydrogenase was also positively interfered, but we failed to calculate the HI threshold. Total bile acid, uric acid, and sodium were all negatively affected, and the HI threshold was 42.23, 500 and 501.8, respectively. Glucose was also negatively interfered, but it failed to achieve the HI threshold. CONCLUSIONS: When the HI value was higher than its threshold, the corresponding analyte was considered inappropriate for reporting. The implementation of the assay-specific HI thresholds could provide an accurate method to identify analytes interfered by hemolysis, which would improve clinical interpretations and further boost laboratory quality by reducing errors associated with hemolysis.
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Análisis Químico de la Sangre/instrumentación , Análisis Químico de la Sangre/métodos , Hemólisis , Pruebas Hematológicas/instrumentación , Hemoglobinas/análisis , HumanosRESUMEN
N6-Methyladenosine (m6A) represents the most prevalent internal modification in mammalian mRNAs. Emerging evidences suggest that m6A modification is profoundly implicated in many biological processes, including cancer development. However, limited knowledge is available about the functional importance of m6A in lung cancer. In this study, by data mining The Cancer Genome Atlas (TCGA) database, we first identified fat mass- and obesity-associated protein (FTO) as a prognostic factor for lung squamous cell carcinoma (LUSC). Then we showed that FTO, but not other m6A modification genes including METTL3, METTL14 and ALKBH5, was the major dysregulated factor responsible for aberrant m6A modification in LUSC. Loss-of-function studies suggested that FTO knockdown effectively inhibited cell proliferation and invasion, while promoted cell apoptosis of L78 and NCI-H520â¯cells. Furthermore, overexpression of FTO, but not its mutant form, facilitated the malignant phenotypes of CHLH-1â¯cells. Mechanistically, FTO enhanced MZF1 expression by reducing m6A levels and mRNA stability in MZF1 mRNA transcript, leading to oncogenic functions. Taken together, our study demonstrates the functional importance of FTO in the tumor progression of LUSC and provides a potential therapeutic target for LUSC treatment.
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Adenosina/análogos & derivados , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Carcinoma de Células Escamosas/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Neoplasias Pulmonares/metabolismo , Adenosina/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/antagonistas & inhibidores , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Factores de Transcripción de Tipo Kruppel/genética , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/genética , Oncogenes , Pronóstico , Estabilidad del ARN , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismoRESUMEN
Curcumin is a natural agent that has ability to dampen tumor cells' growth. However, the natural form of curcumin is prone to degrade and unstable in vitro. Here, we demonstrated that demethoxycurcumin (a curcumin-related demethoxy compound) could inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Moreover, IRS2/PI3K/Akt axis was inactivated in cells treated with demethoxycurcumin. Quantitative real-time reverse transcription polymerase chain reaction demonstrated that miR-551a was down-regulated in ovarian cancer tissues and ovarian cancer cell lines. Over-expression of miR-551a inhibited cell proliferation and induced apoptosis of ovarian cancer cells, whereas down-regulation of miR-551a exerted the opposite function. Luciferase assays confirmed that there was a binding site of miR-551a in IRS2, and we found that miR-551a exerted tumor-suppressive function by targeting IRS2 in ovarian cancer cells. Remarkably, miR-551a was up-regulated in the cells treated with demethoxycurcumin, and demethoxycurcumin suppressed IRS2 by restoration of miR-551a. In conclusion, demethoxycurcumin hindered ovarian cancer cells' malignant progress via up-regulating miR-551a.
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Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Curcumina/análogos & derivados , Proteínas Sustrato del Receptor de Insulina/antagonistas & inhibidores , MicroARNs/biosíntesis , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Adulto , Apoptosis/genética , Sitios de Unión/genética , Carcinoma Epitelial de Ovario , Línea Celular Tumoral , Proliferación Celular/genética , Curcumina/farmacología , Diarilheptanoides , Femenino , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Proteínas Sustrato del Receptor de Insulina/metabolismo , MicroARNs/genética , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Glioblastoma multiforme (GBM) is known as a highly malignant brain tumor with a poor prognosis, despite intensive research and clinical efforts. In this study, we observed that microRNA-873 (miR-873) was expressed at low levels in GBM and that the overexpression of miR-873 dramatically reduced the cell proliferation, migration, and invasion of GBM cells. Our further investigations of the inhibition mechanism indicated that miR-873 negatively affected the carcinogenesis and metastasis of GBM by down-regulating the expression of IGF2BP1, which stabilizes the mRNA transcripts of its target genes. These results demonstrate that miR-873 may constitute a potential target for GBM therapy.
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Neoplasias Encefálicas/patología , Glioblastoma/patología , MicroARNs/fisiología , Metástasis de la Neoplasia , Proteínas de Unión al ARN/genética , Animales , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Glioblastoma/genética , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Regulación hacia ArribaRESUMEN
Upstream stimulatory factor 1 (USF-1) is an important transcription factor that participates in glucose metabolism and tumorigenesis. The aim of the current study was to explore the regulatory mechanism of USF-1 in HepG2 cells exposed to oxygen and glucose deprivation (OGD). After the establishment of the OGD model in HepG2 cells, we determined that the cells treated with OGD exhibited a high apoptotic rate and that the introduction of siRNA against USF-1 protected the cells from OGD-induced apoptosis. The miRNA microarray results demonstrated that a set of miRNAs were deregulated in the cells transfected with USF-1 siRNA, and the set of downregulated miRNAs included a novel miRNA, miR-132. Further analyses indicated that miR-132 overexpression inhibits the protective roles of USF-1 siRNA in OGD-induced apoptosis. We also identified several binding sites for USF-1 in the miR-132 promoter. The silencing of USF-1 resulted in a reduction in miR-132 expression, and USF-1 overexpression increased the expression of this miRNA. Our study indicated that the silencing of USF-1 plays protective roles in OGD-induced apoptosis through the downregulation of miR-132, which indicates that the silencing of USF-1 may be a therapeutic strategy for the promotion of cancer cell survival under OGD conditions.
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Apoptosis , Glucosa/metabolismo , MicroARNs/genética , Oxígeno/metabolismo , Interferencia de ARN , Factores Estimuladores hacia 5'/genética , Regulación hacia Abajo , Células Hep G2 , Humanos , Regiones Promotoras Genéticas , ARN Interferente Pequeño/genéticaRESUMEN
OBJECTIVES: To evaluate the impact of microwave ablation (MWA) on pain relief, quality of life, mobility, and local tumour progression in adult patients with pelvic osteolytic bone metastasis and to test the safety of MWA. METHODS: This study retrospectively analysed the data from 20 patients with pelvic osteolytic metastases who received MWA combined with percutaneous osteoplasty (POP). The visual analogue scale (VAS), musculoskeletal tumour society system (MSTS), and Quality of Life Questionnaire-Bone Metastases 22 (QLQ-BM22) were used to evaluate the pain, limb function, and quality of life. The intraoperative and postoperative complications were recorded. The tumour recurrence and survival time were analysed during the follow-up period (range 3-26 months). RESULTS: All (n = 20) MWA and POP operations were completed successfully. Four patients (20%; 95% CI, 6%-44%) had mild bone cement leakage from surrounding tissues, and there were no obvious symptoms or serious complications. There were significant differences in VAS, MSTS, and QLQ-BM22 scores before and after the operation (P < .001). During the postoperative follow-up period, 9 patients died. The median survival time was 8 months (range 3-26 months; IQR: 4.5-13; 95% CI, 4.2-15.3 months), and the 1-year survival rate was 65% (13/20; 95% CI, 41%-85%). Tumour recurrence occurred in 4 cases (20%; 95% CI, 6%-44%) after the operation, and the median time of recurrence was 12 months (range 8-16 months; IQR: 8.25-12.75; 95% CI, 5.5-18.5 months). CONCLUSIONS: MWA combined with POP is an effective and safe treatment for pelvic osteolytic metastases. It can significantly relieve local pain, reconstruct limb function, improve patients' quality of life, and effectively control local tumour progression. ADVANCES IN KNOWLEDGE: So far, the experience of using microwave in the treatment of pelvic metastases is still limited. MWA combined with POP in the treatment of pelvic osteolytic metastases can provide significant clinical benefits in acceptable low-risk minimally invasive situations and should be provided to patients with appropriate pelvic metastases in a multidisciplinary approach.
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Neoplasias Óseas , Ablación por Catéter , Cementoplastia , Adulto , Humanos , Cuidados Paliativos , Calidad de Vida , Recurrencia Local de Neoplasia/cirugía , Microondas/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Dolor/etiología , Neoplasias Óseas/secundario , Cementoplastia/efectos adversos , Ablación por Catéter/efectos adversosRESUMEN
PI3K inhibitors have emerged as promising therapeutic agents due to their critical role in various cellular processes, particularly in cancer, where the PI3K pathway is frequently dysregulated. This review explores the evolutionary path of PI3K inhibitors from laboratory discovery to clinical application. The journey begins with early laboratory investigations into PI3K signaling and inhibitor development, highlighting fundamental discoveries that laid the foundation for subsequent advancements. Optimization strategies, including medicinal chemistry approaches and structural modifications, are scrutinized for their contributions to enhancing inhibitor potency, selectivity, and pharmacokinetic properties. The translation from preclinical studies to clinical trials is examined, emphasizing pivotal trials that evaluated efficacy and safety profiles. Challenges encountered during clinical development are critically assessed. Finally, the review discusses ongoing research directions and prospects for PI3K inhibitors, underscoring these agents' continuous evolution and therapeutic potential.
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Descubrimiento de Drogas , Fosfatidilinositol 3-Quinasas , Inhibidores de las Quinasa Fosfoinosítidos-3 , Humanos , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3/química , Inhibidores de las Quinasa Fosfoinosítidos-3/síntesis química , Fosfatidilinositol 3-Quinasas/metabolismo , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Estructura Molecular , Relación Estructura-ActividadRESUMEN
Platinum-fluorouracil combination chemotherapy is the standard neoadjuvant treatment for locally advanced gastric cancer in China, but it does not improve the survival benefit of patients. In recent years, the application of immune checkpoint inhibitors and/or targeted drugs in neoadjuvant therapy for gastric cancer has achieved certain efficacy, but the survival benefit of patients is still not obvious. Intra-arterial infusion chemotherapy, as a method of regional therapy, has been widely used in the treatment of many advanced tumors and achieved remarkable curative effect. The role of arterial infusion chemotherapy in neoadjuvant therapy for gastric cancer is not clear. We describe two patients with locally advanced gastric cancer treated with continuous arterial infusion neoadjuvant chemotherapy. Two patients received continuous arterial infusion of chemotherapy drugs for 50 hours, the drugs were pumped into the main feeding artery of the tumor through the arterial catheter. A total of 4 cycles were followed, then undergone surgical resection. The postoperative pathological pCR of two patients was 100%, TRG was 0 grade, and no further anti-tumor therapy was required after operation, achieving clinical cure. During the treatment period, no serious adverse events occurred in either patient. These results suggest that continuous arterial infusion chemotherapy may be a new adjuvant therapy for locally advanced gastric cancer.
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Correction for '6-Gingerol as an arginase inhibitor prevents urethane-induced lung carcinogenesis by reprogramming tumor supporting M2 macrophages to M1 phenotype' by Jingjing Yao et al., Food Funct., 2018, 9, 4611-4620, https://doi.org/10.1039/C8FO01147H.
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Co-administration of vaccines can facilitate the introduction of new vaccines in immunization schedules. This study aimed to evaluate the immunogenicity and safety of co-administration with live attenuated varicella vaccine (VarV) and inactivated hepatitis A vaccine (HepA) among children aged 12 ~ 15 months. In this phase 4 clinical trial, 450 children were randomized with a ratio of 1:1 to receive VarV and Hep A simultaneously (Group A) or separately (Group B). The primary endpoints were the seroconversion rate of anti-varicella-zoster virus (VZV) antibodies 42 days after vaccination of VarV and the seroconversion rate of anti-Hepatitis A virus (HAV) antibodies 30 days after two-dose vaccination of HepA. After full immunization, the seroconversion rates of anti-VZV antibodies were 91.79% in Group A and 92.15% in Group B; the geometric mean titers (GMTs) were 11.80 and 12.19, respectively. The seroconversion rates of anti-HAV antibodies were 99.48% in Group A and 100.0% in Group B; the geometric mean concentrations (GMCs) reached 9499.11 and 9528.36 mIU/ml, respectively. The lower limits of the 95% CI for the seroconversion difference of anti-VZV antibodies and anti-HAV antibodies were -5.86% and -2.90%, which greater than the predefined non-inferiority margin (-10%). The incidence rate of adverse reactions in Group A was lower than Group B (9.33% vs 16.22%), and only one serious adverse event was reported in Group B, which was unrelated to the study vaccine. In conclusion, the co-administration of VarV with HepA has non-inferior immunogenicity and safety profiles were quite comparable with the separate administration of both vaccines.Trial registration number: NCT05526820 (ClinicalTrials.gov).
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Vacuna contra el Herpes Zóster , Vacunas Virales , Niño , Humanos , Vacunas contra la Hepatitis A , Anticuerpos de Hepatitis A , Vacuna contra la Varicela , Vacunas de Productos Inactivados , Anticuerpos Antivirales , Vacunas Atenuadas , Inmunogenicidad VacunalRESUMEN
Toripalimab as a novel PD-1 inhibitor has presented its promising efficacy in patients who developed chemo-refractory carcinomas, whereas no study has ever investigated the effectiveness of toripalimab in chemo-resistant choriocarcinoma. Here we reported the effectiveness and safety data of 4 patients with chemo-resistant choriocarcinoma who underwent PD-1 antibody therapy by toripalimab and individualized chemotherapies. From January 2019 to August 2020, 4 patients with choriocarcinoma were admitted in Shengjing Hospital of China Medical University. The patients' age ranged from 29 to 52 years with a median of 36 years. All the patients achieved CR after the combined therapy of toripalimab with individualized chemotherapies according to the decreased serum ß-hcg level. Two of the four patients were observed with treatment-related adverse events (AEs), including one grade I skin rash and one grade I pruritus. Our cases showed that toripalimab combined with chemotherapy presented a tolerable safety profile and promising effectiveness in patients with chemo-resistant choriocarcinoma, indicating its potential as salvage therapy for this subset of patients.
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ABSTRACT: This study aimed to evaluate the impact of cancer-related mortality on life expectancy in Feicheng City.We extracted the death records and population data of Feicheng City from 2013 to 2018 through the Feicheng Center for Disease Control and Prevention. The mortality, premature mortality, cause-eliminated life expectancy, potential years of life lost (PYLL), average potential years of life lost (APYLL), annual change percentage (APC), and other indicators of cancer were calculated. The age-standardized rates were calculated using the sixth national census (2010).From 2013 to 2018, the mortality rate of cancer in Feicheng City was 221.55/100,000, and the standardized mortality rate was 166.37/100,000. The standardized mortality rate increased from 2013 to 2014 and then decreased annually. The premature mortality of cancer was 8.98% and showed a downward trend (APCâ=â-2.47%, tâ=â-3.10, Pâ=â.04). From 2013 to 2018, the average life expectancy of residents in Feicheng City was 78.63âyears. Eliminating the impact of cancer, life expectancy could increase by 3.72âyears. The rate of life loss caused by cancer in men was higher than that in women. The total life loss caused by cancer deaths was 126,870.50 person-years, the potential life loss rate was 22.51, and the average potential life loss was 13.30âyears. The standardized potential years of life lost rate showed a downward trend (APCâ=â-2.96%, tâ=â-3.72, Pâ=â.02), and APYLL decreased by 1.98% annually (tâ=â-5.44, Pâ=â.01). The top 5 malignant tumors in APYLL were leukemia, breast cancer, brain tumor, liver cancer, and ovarian cancer.Lung cancer, esophageal cancer, female breast cancer, and childhood leukemia have a great impact on the life expectancy of residents in Feicheng City. Effective measures need to be taken to reduce the disease burden of malignant tumors.
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Mortalidad Prematura , Neoplasias/mortalidad , China , Costo de Enfermedad , Femenino , Humanos , Esperanza de Vida , Masculino , Distribución por SexoRESUMEN
BACKGROUND AND OBJECTIVE: We have previously reported that BRCA2 N372 H i.a.1342A>C heterozygous variation presented in platinum-resistant patients. This study aimed to further investigate the mechanism of BRCA2 N372 H mutation in the development of platinum resistance in ovarian cancer. METHODS: The BRCA2 N372 H i.a.1342A>C was synthesized and used to exchange 1 wildtype allele followed by sequencing to confirm the mutant allele sequence. Plasmids were constructed and transfected into the OVCAR-3 cells after lentiviral packaging. BRCA2 N372 H mRNA was detected by qPCR. BRCA2 protein was assessed by immunoblotting. Binding of the BRCA2 to Rad51 was detected by immunofluorescence staining. Sensitivity of the cells to cisplatin treatment was assessed with CCK-8 assay. RESULTS: It was found that expression of BRCA2 protein in ovarian cancer cells transfected with BRCA2 N372 H i.a.1342A>C gene (2.177 ± 0.003) was significantly increased compared to that of the cells transfected with lenti-EGFP only (1.227 ± 0.003, P < 0.001). Binding of the BRCA2 and Rad51 proteins was significantly increased in the cells with BRCA2 N372 H i.a.1342A>C mutation (3.542 ± 0.24) than that in the cells transfected with lenti-EGFP (1.29 ± 0.32) or empty cells (1.363 ± 0.32, P < 0.001). Cell viability significantly increased in the cells transfected with BRCA2 N372 H mutant gene. The IC50 value was significantly higher in the cells transfected with BRCA2 N372 H mutant gene (1.963 ± 0.04) than that of the cells transfected with lenti-EGFP (0.955 ± 0.03, P < 0.01) or empty cells (1.043 ± 0.007, P < 0.01). CONCLUSION: Over expression of mRNA and protein of BRCA2 was detected in the cells with BRCA2 N372 H i.a.1342A>C mutation but not in the lentivirus negative control (lenti-EGFP) or the cells without transfection (empty cells), which may lead to resistance to platinum-based drugs in ovarian cancer cells through homologous recombination repair pathway.
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Alelos , Proteína BRCA2/genética , Cisplatino/farmacología , Mutación , Neoplasias Ováricas/genética , Proteína BRCA2/efectos de los fármacos , Biomarcadores de Tumor , Línea Celular Tumoral , Supervivencia Celular , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos , Femenino , Humanos , Recombinasa Rad51/genética , Recombinasa Rad51/metabolismoRESUMEN
Existing evidence has revealed inconsistent results on the association between metabolic syndrome (MetS) and endometrial cancer (EC) risk. Herein, we aim to better understand this association. Systematic searches of PubMed, EMBASE, and Web of Science through 12 December 2019 were conducted. Observational studies that provided risk estimates of MetS and EC risk were eligible. The quality of the included studies was judged based on the Newcastle-Ottawa scale. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Six studies, comprising 17,772 EC cases and 150,371 participants were included. MetS, diagnosed according to the criteria of the National Cholesterol Education Program-Third Adult Treatment Panel, was associated with an increased risk of EC (OR: 1.62; 95% CI = 1.26-2.07) with substantial heterogeneity (I2 = 78.3%). Furthermore, we found that women with MetS, diagnosed according to the criteria of the International Diabetes Federation, had a significantly higher risk of EC compared to healthy controls (OR: 1.45; 95% CI = 1.16-1.81; I2 = 64.6%). Our findings were generally consistent with the main results in the majority of prespecified subgroups, as well as in sensitivity analyses. In conclusion, MetS is associated with EC risk.