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1.
Clin Oral Investig ; 28(9): 487, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39145865

RESUMO

OBJECTIVE: To assess the influence of unilateral open disc repositioning surgery (ODRS) of the temporomandibular joint (TMJ) on the internal derangement (ID) of the contralateral joint. METHODS: Patients with bilateral ID of TMJ who underwent unilateral ODRS were enrolled and followed-up for one year. They were divided into two groups based on the contralateral disease: the anterior disc displacement with reduction (ADDWR) and without reduction (ADDWoR). Postoperative evaluation included clinical and MRI evaluation. Indices measured were unilateral intermaxillary distance (UID), visual analogue scale (VAS), disc length (DL), condylar height (CH), and disc-condyle angle (DCA). Paired t tests were used to compare the clinical and MRI indices between different time points. RESULTS: Ninety-six patients were enrolled, including 47 in the ADDWR group and 49 in the ADDWoR group. One-year post-surgery, ODRS led to significant increases in MMO, DL, and CH, and decrease in VAS and DCA on the operated side (P < 0.05). In ADDWR group, UID, DL, and CH increased significantly, and VAS decreased (P < 0.05), with no significant change in DCA (P > 0.05). In ADDWoR group, clinical and MRI variables worsened slightly, except for UID, which remained unchanged (P > 0.05). CONCLUSIONS: ODRS is a promising method for correcting TMJ ID and may improve condition of ADDWR and decrease progress of ADDWoR at the contralateral joint. Preoperative bilateral TMJ evaluation is essential for better outcomes. CLINICAL RELEVANCE: ODRS can effectively treat TMJ ID and produce adaptive changes in the contralateral ID, for which continuous monitoring of the contralateral joint is essential.


Assuntos
Imageamento por Ressonância Magnética , Disco da Articulação Temporomandibular , Transtornos da Articulação Temporomandibular , Humanos , Feminino , Masculino , Estudos Prospectivos , Transtornos da Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Adulto , Disco da Articulação Temporomandibular/cirurgia , Disco da Articulação Temporomandibular/diagnóstico por imagem , Resultado do Tratamento , Luxações Articulares/cirurgia , Luxações Articulares/diagnóstico por imagem , Pessoa de Meia-Idade , Medição da Dor , Adolescente
2.
J Cachexia Sarcopenia Muscle ; 14(3): 1312-1321, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36999522

RESUMO

BACKGROUND: Hand grip strength (HGS) is a powerful indicator of sarcopenia and other adverse health outcomes. Normative values for HGS for general Chinese people with a broad age spectrum are lacking. This study aims to establish normative values of HGS and explore the correlations between HGS and body composition among unselected people aged 8-80 in China. METHODS: From 2012 to 2017, 39 655 participants aged 8-80 years in the China National Health Survey were included. Absolute HGS was measured using a Jamar dynamometer. The relative HGS was normalized by body mass index. Body composition indexes included body mass index, body fat percentage, muscle mass, fat mass index (FMI) and muscle mass index (MMI). Sex-specific smoothed centile tables for the P1 , P5 , P25 , P50 , P75 , P95 and P99 centiles of HGS and body composition were generated using lambda-mu-sigma method. The correlations between muscle strength and body composition were estimated by partial Spearman correlation analysis. RESULTS: The median values (25th and 75th percentile) of HGS in boys and girls (8-19 years old) were 22 (14, 34) kg and 18 (12, 22) kg, respectively; in men and women aged 20-80 were 39 (33, 44) kg and 24 (20, 27) kg, respectively. Values of upper and lower HGS across ages had three periods: an increase to a peak in the 20 s in men (with the 5th and 95th values of 30 and 55 kg, respectively) and 30 s in women (with the 5th and 95th values of 18 and 34 kg, respectively), preservation through midlife (20s-40 s), and then a decline after their 50 s. The lowest HGS values in both sexes were in the 70- to 80-year-old group, with the 5th and 95th percentile values of 16 and 40 kg in men, and 10 and 25 kg in women. There were substantial sex differences in body composition in the life course (all P values <0.001). In ageing, the decrease of muscle strength was faster than that of muscle mass in both sexes. The correlations between muscle mass and HGS were most robust than other correlations, especially in women (0.68 vs. 0.50), children and adolescents. CONCLUSIONS: Our study established the age- and sex-specific percentile reference values for hand grip strength in an unselected Chinese population across a broad age-spectrum. The rich data can facilitate the practical appraisal of muscle strength and promote early prediction of sarcopenia and other impairments associated with neuromuscular disorders.


Assuntos
Força da Mão , Sarcopenia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Adulto Jovem , Envelhecimento , População do Leste Asiático , Força da Mão/fisiologia , Inquéritos Epidemiológicos , Sarcopenia/epidemiologia , Pessoa de Meia-Idade
3.
Circ Res ; 130(10): 1490-1506, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35387487

RESUMO

RATIONALE: Long-term exercise provides reliable cardioprotection via mechanisms still incompletely understood. Although traditionally considered a thermogenic tissue, brown adipose tissue (BAT) communicates with remote organs (eg, the heart) through its endocrine function. BAT expands in response to exercise, but its involvement in exercise cardioprotection remains undefined. OBJECTIVE: This study investigated whether small extracellular vesicles (sEVs) secreted by BAT and their contained microRNAs (miRNAs) regulate cardiomyocyte survival and participate in exercise cardioprotection in the context of myocardial ischemia/reperfusion (MI/R) injury. METHODS AND RESULTS: Four weeks of exercise resulted in a significant BAT expansion in mice. Surgical BAT ablation before MI/R weakened the salutary effects of exercise. Adeno-associated virus 9 vectors carrying short hairpin RNA targeting Rab27a (a GTPase required for sEV secretion) or control viruses were injected in situ into the interscapular BAT. Exercise-mediated protection against MI/R injury was greatly attenuated in mice whose BAT sEV secretion was suppressed by Rab27a silencing. Intramyocardial injection of the BAT sEVs ameliorated MI/R injury, revealing the cardioprotective potential of BAT sEVs. Discovery-driven experiments identified miR-125b-5p, miR-128-3p, and miR-30d-5p (referred to as the BAT miRNAs) as essential BAT sEV components for mediating cardioprotection. BAT-specific inhibition of the BAT miRNAs prevented their upregulation in plasma sEVs and hearts of exercised mice and attenuated exercise cardioprotection. Mechanistically, the BAT miRNAs cooperatively suppressed the proapoptotic MAPK (mitogen-associated protein kinase) pathway by targeting a series of molecules (eg, Map3k5, Map2k7, and Map2k4) in the signaling cascade. Delivery of BAT sEVs into hearts or cardiomyocytes suppressed MI/R-related MAPK pathway activation, an effect that disappeared with the combined use of the BAT miRNA inhibitors. CONCLUSIONS: The sEVs secreted by BAT participate in exercise cardioprotection via delivering the cardioprotective miRNAs into the heart. These results provide novel insights into the mechanisms underlying the BAT-cardiomyocyte interaction and highlight BAT sEVs and their contained miRNAs as alternative candidates for exercise cardioprotection.


Assuntos
Vesículas Extracelulares , MicroRNAs , Traumatismo por Reperfusão Miocárdica , Tecido Adiposo Marrom/metabolismo , Animais , Vesículas Extracelulares/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/metabolismo , Condicionamento Físico Animal
4.
Biochem Pharmacol ; 198: 114948, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35192847

RESUMO

Acute myeloid leukemia (AML) is a malignant proliferative disease of myeloid hematopoietic origin and cannot be treated appropriately at present. This is due to the fact that leukemia cells are not sensitive to some of the traditional chemotherapy drugs. Or some chemotherapeutic drugs are too toxic to normal cells, affecting their wide clinical application. In this study, we identified BAM15 as a novel mitochondrial uncoupling agent by screening a library of small molecule compounds that inhibit AML cell activity. BAM15 significantly inhibited proliferation and promoted apoptosis in AML cells while at the same time being less cytotoxic to normal cells. The mechanism may be related to the disturbance of the ROS production balance. In vivo investigations revealed that BAM15 effectively suppressed AML progression and prolonged the survival time of mice. In addition, we found that BAM15 can be used in combination with cytarabine to enhance its anti-cancer activity and inhibit the activity of primary cells in AML. Therefore, we identified BAM15 as a potential drug candidate for the treatment of AML.


Assuntos
Leucemia Mieloide Aguda , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Citarabina/farmacologia , Citarabina/uso terapêutico , Diaminas , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Camundongos , Oxidiazóis , Pirazinas/farmacologia , Espécies Reativas de Oxigênio
5.
Math Biosci Eng ; 19(1): 997-1025, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34903023

RESUMO

Classifying and identifying surface defects is essential during the production and use of aluminum profiles. Recently, the dual-convolutional neural network(CNN) model fusion framework has shown promising performance for defects classification and recognition. Spurred by this trend, this paper proposes an improved dual-CNN model fusion framework to classify and identify defects in aluminum profiles. Compared with traditional dual-CNN model fusion frameworks, the proposed architecture involves an improved fusion layer, fusion strategy, and classifier block. Specifically, the suggested method extracts the feature map of the aluminum profile RGB image from the pre-trained VGG16 model's pool5 layer and the feature map of the maximum pooling layer of the suggested A4 network, which is added after the Alexnet model. then, weighted bilinear interpolation unsamples the feature maps extracted from the maximum pooling layer of the A4 part. The network layer and upsampling schemes ensure equal feature map dimensions ensuring feature map merging utilizing an improved wavelet transform. Finally, global average pooling is employed in the classifier block instead of dense layers to reduce the model's parameters and avoid overfitting. The fused feature map is then input into the classifier block for classification. The experimental setup involves data augmentation and transfer learning to prevent overfitting due to the small-sized data sets exploited, while the K cross-validation method is employed to evaluate the model's performance during the training process. The experimental results demonstrate that the proposed dual-CNN model fusion framework attains a classification accuracy higher than current techniques, and specifically 4.3% higher than Alexnet, 2.5% for VGG16, 2.9% for Inception v3, 2.2% for VGG19, 3.6% for Resnet50, 3% for Resnet101, and 0.7% and 1.2% than the conventional dual-CNN fusion framework 1 and 2, respectively, proving the effectiveness of the proposed strategy.


Assuntos
Alumínio , Redes Neurais de Computação , Análise de Ondaletas
6.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(4): 732-741, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34459174

RESUMO

Robot-assisted fracture reduction usually involves fixing the proximal end of the fracture and driving the distal end of the fracture to the proximal end in a planned reduction path. In order to improve the accuracy and safety of reduction surgery, it is necessary to know the changing rule of muscle force and reduction force during reduction. Fracture reduction force was analyzed based on the muscle force of femoral. In this paper, a femoral skeletal muscle model named as PA-MTM was presented based on the four elements of skeletal muscle model. With this, pinnate angle of the skeletal muscle was considered, which had an effect on muscle force properties. Here, the muscle force of skeletal muscles in different muscle models was compared and analyzed. The muscle force and the change of the reduction force under different reduction paths were compared and simulated. The results showed that the greater the pinnate angle was, the greater the influence of muscle strength was. The biceps femoris short head played a major role in the femoral fracture reduction; the force in the z direction contributed the majority to the resulting force with maximums of 472.18 N and 497.28 N for z and resultant, respectively, and the rationality of the new musculoskeletal model was verified.


Assuntos
Fraturas Ósseas , Procedimentos de Cirurgia Plástica , Fêmur/cirurgia , Humanos , Músculo Esquelético , Tendões
7.
Cancers (Basel) ; 13(14)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34298802

RESUMO

Breast cancer (BC) is a common disease and one of the main causes of death in females worldwide. In the omics era, researchers have used various high-throughput sequencing technologies to accumulate massive amounts of biomedical data and reveal an increasing number of disease-related mutations/genes. It is a major challenge to use these data effectively to find drugs that may protect human health. In this study, we combined the GeneRank algorithm and gene dependency network to propose a precision drug discovery strategy that can recommend drugs for individuals and screen existing drugs that could be used to treat different BC subtypes. We used this strategy to screen four BC subtype-specific drug combinations and verified the potential activity of combining gefitinib and irinotecan in triple-negative breast cancer (TNBC) through in vivo and in vitro experiments. The results of cell and animal experiments demonstrated that the combination of gefitinib and irinotecan can significantly inhibit the growth of TNBC tumour cells. The results also demonstrated that this systems pharmacology-based precision drug discovery strategy effectively identified important disease-related genes in individuals and special groups, which supports its efficiency, high reliability, and practical application value in drug discovery.

8.
World J Gastroenterol ; 27(19): 2366-2375, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34040328

RESUMO

BACKGROUND: Many studies have investigated the relationships between vitamins and esophageal cancer (EC). Most of these studies focused on the roles of vitamins in the prevention and treatment of EC, and few studies have examined the changes in vitamin nutritional status and their influencing factors before and after chemotherapy for EC. Chemotherapy may have a considerable effect on EC patients' vitamin levels and hematological indicators. AIM: To research the nutritional status of multiple vitamins in EC patients during chemotherapy and to assess its clinical significance. METHODS: EC patients admitted to our center from July 2017 to September 2020 were enrolled in this study. Serum concentrations of nine vitamins (A, D, E, B9, B12, B1, C, B2 and B6), hemoglobin, total protein, albumin, blood calcium, blood phosphorus concentrations and body mass index (BMI) were measured in all EC patients. The changes in nine vitamins, hematological indicators and BMI were compared before and after two cycles of chemotherapy. The possible influential factors were analyzed. RESULTS: In total, 203 EC patients receiving chemotherapy were enrolled in this study. Varying degrees of vitamin A, D, C and B2 deficiency and weight loss were found in these patients, and the proportions of vitamin B2 and vitamin C deficiencies increased significantly after chemotherapy (both P < 0.05). Serum concentrations of vitamins A, C, B2 and B6 and BMI before and after chemotherapy were statistically significant (all P < 0.05). Multivariate analysis showed that vitamin A levels significantly differed between male and female EC patients, whereas vitamin D concentration significantly differed in EC patients in different stages (all P < 0.05). Correlations were observed between the changes in serum concentrations of vitamin A and C before and after two cycles chemotherapy and the change in BMI (P < 0.05). Hemoglobin, total protein, serum albumin and blood calcium concentrations significantly decreased in EC patients after chemotherapy (all P < 0.05), while the blood phosphorus level significantly increased after chemotherapy (P < 0.05). Using the difference in vitamin concentrations as the independent variables and the difference in BMI as the dependent variable, logistic regression analysis revealed statistically significant differences for vitamin A, vitamin D and vitamin C (F = 5.082, P = 0.002). CONCLUSION: Vitamin A, D, C and B2 were mainly deficient in patients with EC during chemotherapy. Multivitamin supplementation may help to improve the nutritional status, chemotherapy tolerance and efficacy.


Assuntos
Neoplasias Esofágicas , Vitaminas , Ácido Ascórbico , Neoplasias Esofágicas/tratamento farmacológico , Feminino , Humanos , Masculino , Estado Nutricional , Vitamina A
9.
Neural Regen Res ; 16(9): 1856-1864, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33510093

RESUMO

In vertebrates, most somatosensory pathways begin with the activation of dorsal root ganglion (DRG) neurons. The development of an appropriate DRG culture method is a prerequisite for establishing in vitro peripheral nerve disease models and for screening therapeutic drugs. In this study, we compared the changes in morphology, molecular biology, and transcriptomics of chicken embryo DRG cultured on tissue culture plates (T-DRG) versus three-dimensional collagen hydrogels (C-DRG). Our results showed that after 7 days of culture, the transcriptomics of T-DRG and C-DRG were quite different. The upregulated genes in C-DRG were mainly related to neurogenesis, axon guidance, and synaptic plasticity, whereas the downregulated genes in C-DRG were mainly related to cell proliferation and cell division. In addition, the genes related to cycles/pathways such as the synaptic vesicle cycle, cyclic adenosine monophosphate signaling pathway, and calcium signaling pathway were activated, while those related to cell-cycle pathways were downregulated. Furthermore, neurogenesis- and myelination-related genes were highly expressed in C-DRG, while epithelial-mesenchymal transition-, apoptosis-, and cell division-related genes were suppressed. Morphological results indicated that the numbers of branches, junctions, and end-point voxels per C-DRG were significantly greater than those per T-DRG. Furthermore, cells were scattered in T-DRG and more concentrated in C-DRG, with a higher ratio of 5-ethynyl-2'-deoxyuridine (EdU)-positive cells in T-DRG compared with C-DRG. C-DRG also had higher S100 calcium-binding protein B (S100B) and lower α-smooth muscle actin (α-SMA) expression than T-DRG, and contained fewer terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells after 48 hours of serum starvation. After cryopreservation, C-DRG maintained more intact morphological characteristics, and had higher viability and less TUNEL-positive cells than T-DRG. Furthermore, newly formed nerve bundles were able to grow along the existing Schwann cells in C-DRG. These results suggest that C-DRG may be a promising in vitro culture model, with better nerve growth and anti-apoptotic ability, quiescent Schwann cells, and higher viability. Results from this study provide a reference for the construction, storage, and transportation of tissue-engineered nerves. The study was approved by the Ethics Committee of Aier School of Ophthalmology, Central South University, China (approval No. 2020-IRB16), on March 15, 2020.

10.
Front Public Health ; 8: 177, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32596196

RESUMO

As part of the China National Health Survey, the objective of this study was to explore the prevalence, patterns, and influencing factors of smoking, and understand reasons for smoking cessation among adults in Hebei Province, central China. Using a multi-stage stratified cluster sampling method, 6,552 adults (2,594 males) aged 20-80 were selected in 2017. Demographic, socioeconomic, and tobacco use information were collected by questionnaire interview. The prevalence of ever-smoking, current smoking, and ex-smoking was 28.94, 21.08, and 7.86%, respectively. Male participants had a much higher prevalence of ever-smoking and current smoking (67.39 and 48.77%) than females (3.74 and 2.93%). In male participants, the daily cigarette consumption was 16.61, and the mean age of smoking initiation was 20.95, decreasing with birth year (27.50 in people born before 1946 vs. 17.9 for those born after 1985, p for trend < 0.001). Over 40% of male ever-smokers initiated regular smoking before 20. Compared with never drinking, the ORs (95% CI) of ever-smoking for low, moderate, and high alcohol consumption in male participants were 1.44 (1.11-1.86), 2.80 (1.91-4.11), and 2.40 (1.72-3.33), respectively. Among 479 male ex-smokers, 50.94% stopped smoking because of illness and 49.06% by choice. Among male ex-smokers, hypertensive men were more likely to quit smoking than the normotensive individuals (OR: 1.48, 95% CI: 1.13-1.96). For CVD patients, this effect was estimated as 2.27 (95% CI: 1.56-3.30). This study revealed a high prevalence of ever-smoking, especially in men, in a representative population in central China. Health education focus on tobacco control could be integrated with alcohol consumption reduction to achieve additional benefit.


Assuntos
Fumar , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Prevalência , Fumar/epidemiologia , Adulto Jovem
11.
Molecules ; 24(22)2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718071

RESUMO

Psoralen (P) and isopsoralen (IP) are the main active ingredients in the dried fruit of Psoralen corylifolia L. (PC), with a wide range of pharmacology activities. The intestinal bacteria biotransformation plays a central role in the metabolism of the complex ingredients in traditional Chinese medicine (TCM). Our study aimed to investigated the metabolic profile of P and IP in the intestinal condition, co-cultured with human fecal bacteria anaerobically. Four bio-transforming products were obtained, including 6,7-furano-hydrocoumaric acid (P-1) and 6,7-furano-hydro- coumaric acid methyl ester (P-2), which transformed from P, and 5,6-furano-hydrocoumaric acid (IP-1) and 5,6-furano-hydrocoumaric acid methyl ester (IP-2), which were transformed from IP. It is worth mentioning that IP-2 is a new compound that has not been published. Their structures were analyzed based on their spectroscopic data. Moreover, a highly sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was used to characterize the metabolic pathways of P, IP, and their bio-transforming products in the reaction samples. In addition, the dampening effects against the oxidative stress of P, IP, and their bio-transforming products by human intestinal flora were estimated in vitro via the human colorectal cells (HCT116) and heterogeneous human epithelial colorectal adenocarcinoma cells (Caco-2) cell lines. The results showed that the metabolites have stronger activity than P and IP, which possibly provides a basis for elucidating the treating mechanisms of PC extract against inflammatory bowel disease.


Assuntos
Biotransformação , Ficusina/metabolismo , Furocumarinas/metabolismo , Microbioma Gastrointestinal , Cromatografia Líquida de Alta Pressão , Ficusina/química , Furocumarinas/química , Humanos , Limite de Detecção , Metabolômica/métodos , Estrutura Molecular , Estresse Oxidativo , Espectrometria de Massas em Tandem , Fatores de Tempo
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1585-1591, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607316

RESUMO

OBJECTIVE: To perform genetic analysis, prenatal diagnosis and preimplantation genetic diagnosis (PGD) in a family with a rare deletional ß- thalassemia. METHODS: Hematological parameters of the peripheral blood collected from all the family members were analyzed by whole blood cell analysis and capillary zone electrophoresis (CZE). Polymerase chain reaction-reverse dot blot (PCR-RDB) was used to identify 17 common ß- thalassemia gene mutations, the multiplex ligation-dependent probe amplification (MLPA) and gap-polymerase chain reaction (gap-PCR) were used to identify ß- globin gene cluster deletions. Chorionic villus sample or umbilical cord blood was obtained for prenatal diagnosis. Oligo-cells from blastocyst biopsy were collected for preimplantation genetic diagnosis by whole genome amplification and next generation sequencing. RESULTS: The proband was a carrier of Taiwanese deletion ß- thalassemia, two fetuses were both thalassemia majors. The PGD results showed that 6 of 11 tested embryos could be choose for transplantation. CONCLUSION: The Taiwanese deletion is a rare type deletion of ß- globin gene cluster, and it can lead to thalassemia intermedia or thalassemia major when compounded with other ß- globin gene mutation. PGD is another choice for thalassemia couples.


Assuntos
Diagnóstico Pré-Implantação , Talassemia beta , Feminino , Testes Genéticos , Humanos , Gravidez , Diagnóstico Pré-Natal , Talassemia alfa , Talassemia beta/genética
13.
Front Genet ; 10: 724, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31475034

RESUMO

Immune checkpoint inhibitor (ICI) treatment could bring long-lasting clinical benefits to patients with metastatic cancer. However, only a small proportion of patients respond to PD-1/PD-L1 blockade, so predictive biomarkers are needed. Here, based on DNA methylation profiles and the objective response rates (ORRs) of PD-1/PD-L1 inhibition therapy, we identified 269 CpG sites and developed an initial CpG-based model by Lasso to predict ORRs. Notably, as measured by the area under the receiver operating characteristic curve (AUC), our model can produce better performance (AUC = 0.92) than both a model based on tumor mutational burden (TMB) (AUC = 0.77) and a previously reported TMB model (AUC = 0.71). In addition, most CpGs also have additional synergies with TMB, which can achieve a higher prediction accuracy when joined with TMB. Furthermore, we identified CpGs that are associated with TMB at the individual level. DNA methylation modules defined by protein networks, Kyoto Encylopedia of Genes and Genomes (KEGG) pathways, and ligand-receptor gene pairs are also associated with ORRs. This method suggested novel immuno-oncology targets that might be beneficial when combined with PD-1/PD-L1 blockade. Thus, DNA methylation studies might hold great potential for individualized PD1/PD-L1 blockade or combinatory therapy.

14.
Genes (Basel) ; 10(8)2019 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-31357729

RESUMO

Achieving cancer prognosis and molecular typing is critical for cancer treatment. Previous studies have identified some gene signatures for the prognosis and typing of cancer based on gene expression data. Some studies have shown that DNA methylation is associated with cancer development, progression, and metastasis. In addition, DNA methylation data are more stable than gene expression data in cancer prognosis. Therefore, in this work, we focused on DNA methylation data. Some prior researches have shown that gene modules are more reliable in cancer prognosis than are gene signatures and that gene modules are not isolated. However, few studies have considered cross-talk among the gene modules, which may allow some important gene modules for cancer to be overlooked. Therefore, we constructed a gene co-methylation network based on the DNA methylation data of cancer patients, and detected the gene modules in the co-methylation network. Then, by permutation testing, cross-talk between every two modules was identified; thus, the module network was generated. Next, the core gene modules in the module network of cancer were identified using the K-shell method, and these core gene modules were used as features to study the prognosis and molecular typing of cancer. Our method was applied in three types of cancer (breast invasive carcinoma, skin cutaneous melanoma, and uterine corpus endometrial carcinoma). Based on the core gene modules identified by the constructed DNA methylation module networks, we can distinguish not only the prognosis of cancer patients but also use them for molecular typing of cancer. These results indicated that our method has important application value for the diagnosis of cancer and may reveal potential carcinogenic mechanisms.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Redes Reguladoras de Genes , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Carcinoma/diagnóstico , Carcinoma/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Feminino , Humanos , Melanoma/diagnóstico , Melanoma/genética , Prognóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética
15.
BMJ Open ; 9(2): e025725, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30796128

RESUMO

AIMS: To investigate the prevalence, ethnic differences and associated risk factors for pterygium in Han and Manchu populations aged 40-79 years in Hebei province, China. DESIGN: Cross-sectional study, as a part of the China National Health Survey. SETTING: Hebei province, China. PARTICIPANTS: A multistage cluster sampling method with urbanisation level-based stratification was used to select participants for this study. A total of 4591 individuals over 40 years were recruited for this study. Inclusive criteria: (1) residents who had been living in Hebei for more than 1 year; (2) Han individuals with both parents being Han, or Manchu individuals with both parents being Manchu; (3) underwent ophthalmic examinations and (4) information in the questionnaire was complete. MAIN OUTCOME MEASURES: Multiple logistic regression analysis was used to evaluate the association between pterygium prevalence and factors of interest. RESULTS: A total of 3790 individuals (2351 Hans and 1439 Manchus) met the study criteria, of which 248 were diagnosed with pterygium (6.5%). There was no significant difference between the prevalence rates in Hans (6.2%) and Manchus (7.2%) (p=0.232). Multivariate analysis revealed that the risk factors for grade 2 or higher pterygium were increasing age (p<0.001) and rural residence (OR 1.83; 95% CI 1.11 to 3.02; p=0.018), while the protective factors include gender (female) (OR 0.58; 95% CI 0.37 to 0.88; p=0.011), cigarette smoking (OR 0.53; 95% CI 0.34 to 0.83; p=0.005) and myopia (OR 0.50; 95% CI 0.33 to 0.77; p=0.002). Premature menopause (OR 2.66; 95% CI 1.05 to 6.72; p=0.038) increased the risk of grade 2 or higher pterygium in females, while higher high-density lipoprotein (HDL) (OR 1.94; 95% CI 1.08 to 3.47; p=0.027) was a risk factor of grade 2 or higher pterygium in males. CONCLUSION: The overall prevalence of pterygium in Han and Manchu population in Hebei, China was approximately 6.1%. There were no differences in the prevalence of pterygium between Hans and Manchus, and the race was not a risk factor. This is the first study to report on the positive association between premature menopause and pterygium in females and between higher HDL levels and pterygium in males.


Assuntos
Povo Asiático , Lipoproteínas HDL/sangue , Menopausa Precoce , Pterígio/etnologia , Pterígio/etiologia , Adulto , Fatores Etários , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Medição de Risco/métodos , Fatores de Risco , Fatores Sexuais
16.
J Knee Surg ; 32(8): 804-811, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30206913

RESUMO

The ipsilateral peroneus longus tendon (PLT) was utilized as an autograft for anterior cruciate ligament (ACL) reconstruction of patients with acute ACL rupture and grade III medial collateral ligament (MCL) injury. We investigated the efficacy and safety of this alternative autograft compared with autologous hamstring tendon (HT). Biomechanical testing of the graft options was performed and compared with the native ACL. Thirty-eight patients with acute ACL ruptures and grade III MCL injuries were treated with ACL reconstruction with a doubled autologous PLT or quadrupled autologous HT. Knee stability and function was evaluated clinically with the Lachman test and KT-2000 arthometer as well as subjectively with functional scores. Effects on the donor ankle were evaluated by biomechanical testing. The ultimate tensile strengths of doubled PLT and quadrupled HT were significantly higher than that of the native ACL and the ultimate tensile strength of doubled PLT was comparable with that of quadrupled HT. There were no significant differences in clinical or functional scores between the two groups. There were no significant differences in pre- and postoperative biomechanical testing of the donor ankle. PLT is a suitable alternative autograft for an ACL reconstruction in patients with a concomitant grade III MCL injury without a significant biomechanical disadvantage to the ankle donor site.


Assuntos
Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Tendões/transplante , Adulto , Idoso , Articulação do Tornozelo/fisiologia , Articulação do Tornozelo/cirurgia , Ligamento Cruzado Anterior/cirurgia , Autoenxertos , Feminino , Tendões dos Músculos Isquiotibiais/transplante , Humanos , Articulação do Joelho/fisiologia , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Transplante Autólogo
17.
Genes (Basel) ; 8(7)2017 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-28708071

RESUMO

The cancer atavistic theory suggests that carcinogenesis is a reverse evolution process. It is thus of great interest to explore the evolutionary origins of cancer driver genes and the relevant mechanisms underlying the carcinogenesis. Moreover, the evolutionary features of cancer driver genes could be helpful in selecting cancer biomarkers from high-throughput data. In this study, through analyzing the cancer endogenous molecular networks, we revealed that the subnetwork originating from eukaryota could control the unlimited proliferation of cancer cells, and the subnetwork originating from eumetazoa could recapitulate the other hallmarks of cancer. In addition, investigations based on multiple datasets revealed that cancer driver genes were enriched in genes originating from eukaryota, opisthokonta, and eumetazoa. These results have important implications for enhancing the robustness of cancer prognosis models through selecting the gene signatures by the gene age information.

18.
BMC Cancer ; 16: 171, 2016 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-26926340

RESUMO

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been reported to promote tumorigenesis and progression in several human malignancies. The purpose of this study was to explore the function of BDNF in lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC). METHODS: The expression of BDNF was examined in 110 samples of lung SCC and ADC by immunohistochemistry. The protein level of BDNF was examined in 25 lung SCC or ADC samples and paired non-tumors by western blot. BDNF expression was also evaluated in human bronchial epithelial cells (HBE) and 4 lung cancer cell lines using western blot. Three BDNF mRNA variants containing exons IV, VI and IX were evaluated in HBE, two SCC (SK, LK2) and two ADC (A549, LTE) cell lines by RT-PCR. The expression and secretion of BDNF were also determined in cells using western blot and ELISA. Then the shRNA specific for BDNF was transfected into LK2 or A549 cells to further elucidate the BDNF knockdown on cell proliferation, apoptosis and invasion, which were confirmed by MTT, flow cytometry and transwell examinations. RESULTS: 71.8 % (79 out of 110) of lung SCC and ADC samples were detected positive BDNF, and high expression of BDNF was significantly correlated with histological type and T stage. Compared with non-tumorous counterparts, BDNF was apparently overexpressed in SCC and ADC tissues. In cell studies, the extensive expression and secretion of BDNF were demonstrated in lung cancer cells compared with HBE cells. Interestingly, the expressions of BDNF mRNA variant IV and VI were identical in all cells examined. However, more expression of BDNF mRNA variant IX was found in SK and LK2 cells. The apoptotic cells were increased, and the cell proliferation and invasion were both attenuated once the expression of BDNF was inhibited. When retreated by rhBDNF, BDNF knockdown cells showed less apoptotic or more proliferative and invasive. CONCLUSIONS: Our data show that BDNF probably facilitates the tumorigenesis of lung SCC and ADC. The expression of BDNF mRNA variant IX is probably more helpful to the upregulation of BDNF in SCC, and intervening the production of BDNF could be a possible strategy to lung cancer therapy.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Pulmonares/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Apoptose/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Carga Tumoral
19.
AIDS Res Ther ; 13: 3, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26793263

RESUMO

BACKGROUND: Since the first HIV-1 case in 1989, Hebei province has presented a clearly rising trend of HIV-1 prevalence, and HIV-1 genetic diversity has become the vital barrier to HIV prevention and control in this area. To obtain detailed information of HIV-1 spread in different populations and in different areas of Hebei, a cross-sectional HIV-1 molecular epidemiological investigation was performed across the province. METHODS: Blood samples of 154 newly diagnosed HIV-1 individuals were collected from ten prefectures in Hebei using stratified sampling. Partial gag and env genes were amplified and sequenced. HIV-1 genotypes were identified by phylogenetic tree analyses. RESULTS: Among the 139 subjects genotyped, six HIV-1 subtypes were identified successfully, including subtype B (41.0 %), CRF01_AE (40.3 %), CRF07_BC (11.5 %), CRF08_BC (4.3 %), unique recombinant forms (URFs) (1.4 %) and subtype C (1.4 %). Subtype B was identified as the most frequent subtype. Two URF recombination patterns were the same as CRF01_AE/B. HIV-1 genotype distribution showed a significant statistical difference in different demographic characteristics, such as source (P < 0.05), occupation (P < 0.05) and ethnicity (P < 0.05). The distributions of subtype B (P < 0.05), CRF01_AE (P < 0.05), CRF07_BC (P < 0.05) and subtype C (P < 0.05) showed significant differences in all ten prefectures, and the distributions of all six subtypes were significantly different in Shijiazhuang (P < 0.05) and Xingtai (P < 0.05), but not in other prefectures (P > 0.05). The differences in HIV-1 genotype distribution were closely associated with transmission routes. Particularly, all six subtype strains were found in heterosexuals, showing that HIV-1 has spread from the high-risk populations to the general populations in Hebei, China. In addition, CRF01_AE instead of subtype B has become the major strain of HIV-1 infection among homosexuals. CONCLUSIONS: Our study revealed HIV-1 evolution and genotype distribution by investigating newly diagnosed HIV-1 individuals in Hebei, China. This study provides important information to enhance the strategic plan for HIV prevention and control in China.


Assuntos
Infecções por HIV/genética , HIV-1/genética , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Produtos do Gene env/genética , Produtos do Gene gag/genética , Variação Genética/genética , Genótipo , Infecções por HIV/epidemiologia , Humanos , Masculino , Filogenia , Análise de Sequência de DNA , Adulto Jovem
20.
Zhonghua Yi Xue Za Zhi ; 90(29): 2078-81, 2010 Aug 03.
Artigo em Chinês | MEDLINE | ID: mdl-21029651

RESUMO

OBJECTIVE: To study the expression of cell cycle related factor Gli2 in autogenous vein graft and its relation with neointima formation. METHOD: Autogenous vein graft model were established in 36 male wistar rats of 8 weeks old, 140 g, by transplanting the left jugular vein to intra renal abdominal aorta with microsurgical technique. Graft veins were harvest at 14, 28 days after transplantation. The IF and W-B were used to detect the protein expression in the vein graft. At the same time Gli2- mRNA was measured by RT-PCR. RESULTS: Immunofluorescent staining showed that the Gli2+ cells was only 3.2% ± 0.4% in the normal vein, but was much more in the vein graft after surgery, was 41.3% ± 0.6%, 58.3 ± 0.6% respectively; The expression of Gli2 and PCNA were both elevated in the vein graft. There is a positive correlation between them which indicated by W-B, the relation index was 0.826; the Gli2 mRNA content was also increased in vein graft, was 8.9, 13.6 fold compared with normal vein as 1 respectively. CONCLUSION: Gli2 is upregulated in autogenous vein grafts and may correlated with the proliferation of vascular smooth muscle cells.


Assuntos
Fatores de Transcrição Kruppel-Like/metabolismo , Túnica Íntima/metabolismo , Veias/metabolismo , Veias/transplante , Animais , Masculino , Ratos , Ratos Wistar , Transplante Autólogo , Túnica Íntima/patologia , Proteína Gli2 com Dedos de Zinco
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