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BACKGROUND: Monopolar spindle-binding protein 3B (MOB3B) functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers. AIM: To investigate the role of MOB3B in colorectal cancer (CRC). METHODS: This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis. After overexpression and knockdown of MOB3B expression were induced in CRC cell lines, changes in cell viability, migration, invasion, and gene expression were assayed. Tumor cell autophagy was detected using transmission electron microscopy, while nude mouse xenograft experiments were performed to confirm the in-vitro results. RESULTS: MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis. Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells, whereas knockdown of MOB3B expression had the opposite effects in CRC cells. At the molecular level, microtubule-associated protein light chain 3 II/I expression was elevated, whereas the expression of matrix metalloproteinase (MMP)2, MMP9, sequestosome 1, and phosphorylated mechanistic target of rapamycin kinase (mTOR) was downregulated in MOB3B-overexpressing RKO cells. In contrast, the opposite results were observed in tumor cells with MOB3B knockdown. The nude mouse data confirmed these in-vitro findings, i.e., MOB3B expression suppressed CRC cell xenograft growth, whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts. CONCLUSION: Loss of MOB3B expression promotes CRC development and malignant behaviors, suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.
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Autofagia , Movimento Celular , Neoplasias Colorretais , Invasividade Neoplásica , Transdução de Sinais , Serina-Treonina Quinases TOR , Idoso , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , Serina-Treonina Quinases TOR/metabolismoRESUMO
Introduction: Cancer, particularly lung cancer, is a significant global healthcare challenge. Non-Small Cell Lung Cancer (NSCLC) constitutes 85% of cases. Patients often seek alternative therapies like Chinese medicine alongside Western treatments. This study investigates the survival outcomes and cost-effectiveness of adjunctive Chinese medicine therapy for NSCLC patients in Taiwan. Methods: We utilized the National Health Insurance Research Database in a retrospective cohort study from 2000 to 2018, focusing on NSCLC patients diagnosed between 2007 and 2013. After propensity score matching 1:5 ratio, then compared patients with and without adjunctive Chinese medicine therapy. Survival outcomes, cost-effectiveness, and sensitivity analyses were conducted. Results: The study involved 43,122 NSCLC patients with 5.76% receiving adjunctive Chinese medicine. There is no significant associated between the risk of death and adjuvant Chinese medicine therapy until 181-365 days of adjuvant treatment could reduce the risk of death (HR = 0.88, 95% CI: 0.80-0.98). Cost-effectiveness analysis showed an incremental cost-effectiveness ratio of 880,908 NT$/year. Conclusion: Adjunctive Chinese medicine therapy, particularly when administered for 181-365 days, significantly reduced the mortality risk among stage IV NSCLC patients. The cost-effectiveness aligns with willingness-to-pay thresholds, indicating economic benefit.
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OBJECTIVE: To investigate the use of anti-osteoporotic agents and refracture incidence in patients with osteoporotic vertebral compression fracture (OVCF) following percutaneous vertebral augmentation (PVA) and to evaluate the real-world treatment of patients using denosumab following PVA. This study aims to provide spine surgeons with empirical insights derived from real-world scenarios to enhance the management of bone health in OVCF patients. METHODS: This retrospective cohort study was based on data from the MarketScan and Optum databases from the USA. Female patients aged 55-90 years who underwent PVA for OVCF between January 2013 and March 2020 were included and followed up from the day after surgery. Patients who received at least one dose of denosumab were included in the denosumab cohort and were further divided into the on-treatment and off-treatment groups according to whether they received a second dose of denosumab, with follow-up beginning on the index day (225 days after the first denosumab dose). In this study, the off-treatment group was considered as the control group. Refracture incidence after PVA, the proportion of patients using anti-osteoporotic agents in the total study population, and refracture incidence after the index day in the denosumab cohort were analyzed. RESULTS: A total of 13,451 and 21,420 patients from the MarketScan and Optum databases, respectively, were included. In the denosumab cohort, the cumulative incidence of clinical osteoporotic fractures within 3 years after the index day was significantly lower in the on-treatment group than in the off-treatment group (MarketScan database: 23.0% vs 39.0%, p = 0.002; Optum database: 28.2% vs 40.0%, p = 0.023). The cumulative incidence of clinical vertebral fractures was also lower in the on-treatment group than in the off-treatment group, with a significant difference in the MarketScan database (14.4% vs 25.5%, p = 0.002) and a numerical difference was found in the Optum database (20.2% vs 27.5%, p = 0.084).The proportion of patients using anti-osteoporotic agents was low at 6 months postoperatively, with only approximately 7% using denosumab and 13%-15% taking oral bisphosphonates. CONCLUSION: Postmenopausal women have a high refracture rate and a low proportion of anti-osteoporotic drug use after PVA. Continued denosumab treatment after PVA is associated with a lower risk of osteoporotic and clinical vertebral fractures. Therefore, denosumab may be a treatment option for patients with osteoporosis after PVA.
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Conservadores da Densidade Óssea , Denosumab , Fraturas por Compressão , Fraturas por Osteoporose , Recidiva , Fraturas da Coluna Vertebral , Vertebroplastia , Humanos , Feminino , Idoso , Denosumab/uso terapêutico , Estudos Retrospectivos , Pessoa de Meia-Idade , Fraturas da Coluna Vertebral/prevenção & controle , Fraturas da Coluna Vertebral/cirurgia , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/uso terapêutico , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/cirurgia , Vertebroplastia/métodos , Fraturas por Compressão/cirurgia , IncidênciaRESUMO
Obesity is accompanied by multiple known health risks and increased morbidity, and obese men display reduced reproductive health. However, the impact of obesity on the testes at the molecular levels remain inadequately explored. This is partially attributed to the lack of monitoring tools for tracking alterations within cell clusters in testes associated with obesity. Here, we utilized single-cell RNA sequencing to analyze over 70,000 cells from testes of obese and lean mice, and to study changes related to obesity in non-spermatogenic cells and spermatogenesis. The Testicular Library encompasses all non-spermatogenic cells and spermatogenic cells spanning from spermatogonia to spermatozoa, which will significantly aid in characterizing alterations in cellular niches and the testicular microenvironment during high-fat diet (HFD)-induced obesity. This comprehensive dataset is indispensable for studying how HFD disrupts cell-cell communication networks within the testis and impacts alterations in the testicular microenvironment that regulate spermatogenesis. Being the inaugural dataset of single-cell RNA-seq in the testes of diet-induced obese (DIO) mice, this holds the potential to offer innovative insights and directions in the realm of single-cell transcriptomics concerning male reproductive injury associated with HFD.
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Dieta Hiperlipídica , Obesidade , Análise de Célula Única , Testículo , Transcriptoma , Animais , Masculino , Dieta Hiperlipídica/efeitos adversos , Camundongos , Testículo/metabolismo , Obesidade/genética , Obesidade/etiologia , EspermatogêneseRESUMO
Intervertebral disc degeneration (IVDD) is a worldwide disease that causes low back pain and reduces quality of life. Biotherapeutic strategies based on tissue engineering alternatives, such as intervertebral disc scaffolds, supplemented by drug-targeted therapy have brought new hope for IVDD. In this study, to explore the role and mechanism of MnO2/GelMA composite hydrogels in alleviating IVDD, we prepared composite hydrogels with MnO2 and methacrylate gelatin (GelMA) and characterized them using compression testing and transmission electron microscopy (TEM). Annulus fibrosus cells (AFCs) were cultured in the composite hydrogels to verify biocompatibility by live/dead and cytoskeleton staining. Cell viability assays and a reactive oxygen species (ROS) probe were used to analyze the protective effect of the composite hydrogels under oxidative damage. To explore the mechanism of improving the microenvironment, we detected the expression levels of antioxidant and autophagy-related genes and proteins by qPCR and Western blotting. We found that the MnO2/GelMA composite hydrogels exhibited excellent biocompatibility and a porous structure, which promoted cell proliferation. The addition of MnO2 nanoparticles to GelMA cleared ROS in AFCs and induced the expression of antioxidant and cellular autophagy through the common SIRT1/NRF2 pathway. Therefore, the MnO2/GelMA composite hydrogels, which can improve the disc microenvironment through scavenging intracellular ROS and resisting oxidative damage, have great application prospects in the treatment of IVDD.
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Purpose: Minimally invasive therapies (MIT) have gained popularity due to their capacity to reduce trauma, enhance aesthetic outcomes, and shorten recovery periods. This article explores patients' perceptions and preferences regarding MIT for varicose veins (VVs) while analyzing associated influencing factors to provide a better understanding. Patients and methods: A cross-sectional survey at Zhejiang Rongjun Hospital was performed from January 2022 to June 2023, involving 305 participants with VVs. The questionnaire assessed patient demographics, VVs severity, prior treatment experiences, and treatment preferences. Statistical analyses, including chi-square and Kruskal-Wallis tests, were conducted to explore the correlations between patient characteristics, treatment preferences, and factors influencing these choices. Results: Nearly half of the participants (44.3%) lacked information on any surgical options, whereas a slight majority (55.7%) possessed familiarity with at least one treatment modality, and only 9.8% knew of all six treatment methods presented. Patient surveys discerned that the majority (68.5%) declared an inadequate grasp of treatment methodologies to articulate a treatment preference. Among the 96 patients who made a treatment choice, 24.0% opted for traditional surgery, while 76.0% chose MIT and a higher preference for MIT among male patients compared to female patients (p = 0.006). The patients preferred treatment options for VVs significantly affected by vascular surgeon recommendations and the number of follow-up visits (r = 0.129, p = 0.024; r = 0.122, p = 0.033). Conclusion: The study highlights limited awareness of MIT among Chinese patients with VVs. The insights emphasize the influential role of vascular surgeons' recommendations and suggest a growing predilection for less invasive treatments due to their advantages in recovery and aesthetics. Provider-patient communication, including education about available treatments and shared decision-making, is essential to align treatment plans with patient expectations and improve outcomes.
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Background: A serious consequence of diabetes is diabetic nephropathy (DN), which is commonly treated by statins. Studies evaluating the effects of statin medication have yielded inconsistent results regarding the potential association with diabetic nephropathy. To manage diabetic nephropathy's onset and improve the quality of life of patients, it is imperative to gain a comprehensive understanding of its contributing factors. Data and methods: Our study was conducted using the National Health and Nutrition Examination Survey (NHANES) as well as weighted multivariate logistic regression models to determine the odds ratio (OR) and 95% confidence intervals (95%CI) for diabetic nephropathy. We conducted stratified analyses to examine the impact of statins and the duration of their usage on diabetic nephropathy in different subgroups. A nomogram model and the receiver operating characteristic (ROC) curve were also developed to predict DN risk. Results: Statin use significantly increased the incidence of DN (OR=1.405, 95%CI (1.199,1.647), p<0.001). Individuals who used statins for 5 to 7 years were more likely to develop diabetic nephropathy (OR=1.472, 95%CI (1.057,2.048), p=0.022) compared to those who used statins for 1-3 years (OR=1.334, 95%CI (1.058,1.682), p=0.015) or <1 year (OR=1.266, 95%CI (1.054,1.522), p = 0.012). Simvastatin has a greater incidence of diabetic nephropathy (OR=1.448, 95%CI(1.177, 1.78), P < 0.001). Conclusion: Taking statins long-term increases the risk of DN. Statin use is associated with an increased risk of DN. Caution should be exercised when prescribing atorvastatin and simvastatin for long-term statin therapy.
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Nefropatias Diabéticas , Inibidores de Hidroximetilglutaril-CoA Redutases , Inquéritos Nutricionais , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto , Idoso , Incidência , Fatores de RiscoRESUMO
The general strategy for n-type organic thermoelectric is to blend n-type conjugated polymer hosts with small molecule dopants. In this work, all-polymer n-type thermoelectric is reported by dissolving a novel n-type conjugated polymer and a polymer dopant, poly(ethyleneimine) (PEI), in alcohol solution, followed by spin-coating to give polymer host/polymer dopant blend film. To this end, an alcohol-soluble n-type conjugated polymer is developed by attaching polar and branched oligo (ethylene glycol) (OEG) side chains to a cyano-substituted poly(thiophene-alt-co-thiazole) main chain. The main chain results in the n-type property and the OEG side chain leads to the solubility in hexafluorineisopropanol (HFIP). In the polymer host/polymer dopant blend film, the Coulombic interaction between the dopant counterions and the negatively charged polymer chains is reduced and the ordered stacking of the polymer host is preserved. As a result, the polymer host/polymer dopant blend exhibits the power factor of 36.9 µW m-1 K-1, which is one time higher than that of the control polymer host/small molecule dopant blend. Moreover, the polymer host/polymer dopant blend shows much better thermal stability than the control polymer host/small molecule dopant blend. This research demonstrates the high performance and excellent stability of all-polymer n-type thermoelectric.
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In this systematic review and meta-analysis, the diagnostic performance of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT was compared with that of 18F-DCFPyL PET for patients with suspected prostate cancer (PCa). Up to September 2023, the PubMed, Embase and Web of Science databases were thoroughly searched for relevant papers. Studies examining the diagnostic performance of 18F-DCFPyL PET and 68Ga-PSMA PET/CT in patients with suspected PCa were included in the present review. The Quality Assessment of Diagnostic Performance Studies-2 tool was used to rate the diagnostic performance of each study. The diagnostic performance of 18F-DCFPyL PET and 68Ga-PSMA PET/CT for primary PCa was examined by 13 studies included, comprising 1,178 patients. The pooled sensitivity and specificity of 18F-DCFPyL PET were 0.92 (95% CI, 0.85-0.96) and 0.59 (95% CI, 0.08-0.96), respectively. For 68Ga-PSMA PET/CT, the pooled sensitivity and specificity were 0.96 (95% CI, 0.88-0.99) and 0.71 (95% CI, 0.57-0.82), respectively. 18F-DCFPyL PET and 68Ga-PSMA PET/CT both had an area under the receiver operating characteristic curve of 0.92 (95% CI, 0.89-0.94). In addition, the Fagan nomogram revealed that the post-test probabilities for 18F-DCFPyL PET and 68Ga-PSMA PET/CT could rise to 69 and 77% when the pre-test probability was set at 50%. In conclusion, a comparable diagnostic performance for patients with suspected PCa was determined for 18F-DCFPyL PET and 68Ga-PSMA PET/CT. However, it is crucial to keep in mind that the findings of the present meta-analysis come from investigations with modest sample sizes. Therefore, more extensive research is required to obtain more solid data.
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Células Matadoras Naturais , Linfoma , Humanos , Estudos Retrospectivos , Linfoma/patologiaRESUMO
PURPOSE: We aimed to explore the relationship between bone mineral density (BMD), bone metabolism markers, and blood lipid-related indicators, body mass index (BMI) in elderly individuals. METHODS: A retrospective analysis was conducted on 710 patients. Patients' gender, age, height, weight, bone density values, T-scores, bone metabolism markers (including serum N-terminal propeptide of type I collagen (s-PINP), serum C-terminal telopeptide of type I collagen (s-CTX) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and lipid-related indicators (including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and Castelli index 1 (TC/HDL-C index) and Castelli index 2 (LDL-C/HDL-C index) were recorded. Correlations between variables were analyzed, and patients were grouped according to gender and T-score for intergroup comparisons. RESULTS: HDL-C negatively correlates with BMD and s-CTX. TG, Castelli index, and BMI positively correlate with BMD. BMI negatively correlates with s-PINP. 1,25(OH)2D3 negatively correlates with TC, LDL-C, and Castelli index. LDL-C positively correlates with BMD in males, and TC negatively correlates with s-PINP. In females, HDL-C negatively correlates with BMD, and s-CTX positively correlates with Castelli index. 1,25(OH)2D3 negatively correlates with TC, LDL-C, and Castelli index. TG and Castelli index were higher in normal bone mass group, while HDL-C is higher in the osteoporosis group. TG and BMI positively predicted bone mass density, while HDL-C negatively predicted bone mass density. CONCLUSIONS: HDL-C may have a predictive role in osteoporosis, particularly in women. The likelihood of osteoporosis is lower in individuals with high BMI or hyperlipidemia. Some lipid metabolism markers can be used to predict osteoporosis, and further research is needed.
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Densidade Óssea , Osteoporose , Masculino , Humanos , Feminino , Idoso , LDL-Colesterol , Índice de Massa Corporal , Metabolismo dos Lipídeos , Estudos Retrospectivos , Triglicerídeos , Lipídeos , Osteoporose/diagnóstico por imagem , HDL-ColesterolRESUMO
The senescence-associated secretory phenotype (SASP) is a generic term for the secretion of cytokines, such as pro-inflammatory factors and proteases. It is a crucial feature of senescent cells. SASP factors induce tissue remodeling and immune cell recruitment. Previous studies have focused on the beneficial role of SASP during embryonic development, wound healing, tissue healing in general, immunoregulation properties, and cancer. However, some recent studies have identified several negative effects of SASP on fracture healing. Senolytics is a drug that selectively eliminates senescent cells. Senolytics can inhibit the function of senescent cells and SASP, which has been found to have positive effects on a variety of aging-related diseases. At the same time, recent data suggest that removing senescent cells may promote fracture healing. Here, we reviewed the latest research progress about SASP and illustrated the inflammatory response and the influence of SASP on fracture healing. This review aims to understand the role of SASP in fracture healing, aiming to provide an important clinical prevention and treatment strategy for fracture. Clinical trials of some senolytics agents are underway and are expected to clarify the effectiveness of their targeted therapy in the clinic in the future. Meanwhile, the adverse effects of this treatment method still need further study.
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Consolidação da Fratura , Fraturas Ósseas , Feminino , Gravidez , Humanos , Fenótipo Secretor Associado à Senescência , Senoterapia , CitocinasRESUMO
BACKGROUND: To date, few reports have evaluated the long-term outcome of percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs) and the factors influencing the long-term outcome of this procedure are uncertain. METHODS: A total of 91 patients underwent PKP for thoracolumbar OVCFs from June 2012 to December 2012. Pain Visual Analogue Scores (VAS) and Oswestry Disability Index (ODI) were recorded preoperatively and after 10-year follow-up. Factors that may affect surgical outcome, such as gender, age, height, weight, hypertension, diabetes, cause of injury, fracture segment, length of hospitalization, history of previous spinal surgery, preoperative bone mineral density (BMD), preoperative VAS and ODI scores, length of surgery, bone cement dosage, postoperative standardized anti-osteoporosis treatment, and other new vertebral fractures, were analyzed by multiple linear regression with VAS and ODI scores at the last follow-up. The correlation factors affecting the efficacy were analyzed. RESULTS: The preoperative and final follow-up pain VAS was 7.9 ± 1.1 and 2.2 ± 1.1. ODI scores were 30.4 ± 4.2 and 10.7 ± 2.6. The difference was statistically significant (P < 0.05). Most of the patients were females aged 65-75 years who suffered low-energy injuries, with most of the fracture segments in the thoracolumbar region (T11-L2). At the final follow-up visit, 12 cases (13.19%) developed other new vertebral fractures, and 33 cases (36.26%) continued to adhere to anti-osteoporosis treatment after discharge. Multiple linear regression analysis showed that there was a statistical difference between gender and VAS score at the last follow-up (P < 0.05), and between age, cause of injury and postoperative standardized anti-osteoporosis treatment and ODI at the last follow-up (P < 0.05). There were no statistically significant differences between the other factors and the final follow-up VAS and ODI scores (P > 0.05). CONCLUSION: The long-term outcome after PKP is satisfactory. Age, gender, cause of injury, and standardized postoperative anti-osteoporosis treatment may be factors affecting the long-term outcome.
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Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Feminino , Humanos , Masculino , Cifoplastia/métodos , Seguimentos , Fraturas por Compressão/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Cimentos Ósseos/uso terapêutico , Fraturas por Osteoporose/cirurgia , Dor/complicações , Dor/tratamento farmacológicoRESUMO
The development of 1,8-naphthalimide derivatives as cell probes, DNA targeting agents, and anti-tumor drugs is one of the research hotspots in the field of medicine. Naphthalimide compounds are a kind of DNA embedder, which can change the topological structure of DNA by embedding in the middle of DNA base pairs, and then affect the recognition and action of topoisomerase on DNA. Aminofide and mitonafide are the first 2 drugs to undergo clinical trials. They have good DNA insertion ability, can embed DNA double-stranded structure, and induce topoisomerase II to cut part of pBR322DNA, but not yet entered the market due to their toxicity. In this paper, the design and structure-activity relationship of mononaphthalimide and bisaphthalimide compounds were studied, and the relationship between the structure of naphthalimide and anti-tumor activity was analyzed and discussed. It was found that a variety of structural modifications were significant in improving anti-tumor activity and reducing toxicity.
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Antineoplásicos , Neoplasias , Humanos , Naftalimidas/farmacologia , Naftalimidas/química , Naftalimidas/uso terapêutico , Relação Estrutura-Atividade , Neoplasias/tratamento farmacológico , Neoplasias/genética , DNA/genética , DNA/química , DNA/uso terapêutico , Antineoplásicos/uso terapêutico , Linhagem Celular TumoralRESUMO
CONTEXT.: Eosinophilic solid and cystic renal cell carcinoma is now defined in the 5th edition of the 2022 World Health Organization classification of urogenital tumors. OBJECTIVE.: To perform morphologic, immunohistochemical, and preliminary genetic studies about this new entity in China for the purpose of understanding it better. DESIGN.: The study includes 18 patients from a regional tertiary oncology center in northern China (Tianjin, China). We investigated the clinical and immunohistochemical features of these cases. RESULTS.: The mean age of patients was 49.6 years and the male to female ratio was 11:7. Macroscopically, 1 case had the classic cystic and solid appearance whereas the others appeared purely solid. Microscopically, all 18 tumors shared similar solid and focal macrocystic or microcystic growth pattern, and the cells were characterized by voluminous and eosinophilic cytoplasm, along with coarse amphophilic stippling. Immunohistochemically, most of the tumors had a predominant cytokeratin (CK) 20-positive feature, ranging from focal cytoplasmic staining to diffuse membranous accentuation. Initially, we separated these cases into different immunohistochemical phenotypes. Group 1 (7 of 18; 38.5%) was characterized by positive phospho-4EBP1 and phospho-S6, which can imply hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. Group 2 (4 of 18; 23%) was negative for NF2, probably implying a germline mutation of NF2. Group 3 (7 of 18; 38.5%) consisted of the remaining cases. One case had metastatic spread and exhibited an aggressive clinical course, and we detected cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation in this case; other patients were alive and without disease progression. CONCLUSIONS.: Our research proposes that eosinophilic solid and cystic renal cell carcinoma exhibits prototypical pathologic features with CK20 positivity and has aggressive potential.
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The global transition towards diets high in calories has contributed to 2.1 billion people becoming overweight, or obese, which damages male reproduction and harms offspring. Recently, more and more studies have shown that paternal exposure to stress closely affects the health of offspring in an intergenerational and transgenerational way. SET Domain Containing 2 (SETD2), a key epigenetic gene, is highly conserved among species, is a crucial methyltransferase for converting histone 3 lysine 36 dimethylation (H3K36me2) into histone 3 lysine 36 trimethylation (H3K36me3), and plays an important regulator in the response to stress. In this study, we compared patterns of SETD2 expression and the H3K36me3 pattern in pre-implantation embryos derived from normal or obese mice induced by high diet. The results showed that SETD2 mRNA was significantly higher in the high-fat diet (HFD) group than the control diet (CD) group at the 2-cell, 4-cell, 8-cell, and 16-cell stages, and at the morula and blastocyst stages. The relative levels of H3K36me3 in the HFD group at the 2-cell, 4-cell, 8-cell, 16-cell, morula stage, and blastocyst stage were significantly higher than in the CD group. These results indicated that dietary changes in parental generation (F0) male mice fed a HFD were traceable in SETD2/H3K36me3 in embryos, and that a paternal high-fat diet brings about adverse effects for offspring that might be related to SETD2/H3K36me3, which throws new light on the effect of paternal obesity on offspring from an epigenetic perspective.
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Dieta Hiperlipídica , Histonas , Humanos , Masculino , Animais , Camundongos , Histonas/genética , Histonas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Lisina/metabolismo , Obesidade/genética , Desenvolvimento EmbrionárioRESUMO
The ability of n-type polymer thermoelectric materials to tolerate high doping loading limits further development of n-type polymer conductivity. Herein, two alcohol-soluble n-type polythiophene derivatives that are n-PT3 and n-PT4 are reported. Due to the ability of two polymers to tolerate doping loading more significantly than 100 mol%, both achieve electrical conductivity >100 S cm-1 . Moreover, the conductivity of both polythiophenes remains almost constant at high doping concentrations with excellent doping tunability, which may be related to their ability to overcome charging-induced backbone torsion and morphology change caused by saturated doping. The characterizations reveal that n-PT4 has a high doping level and carrier concentration (>3.10 × 1020 cm-3 ), and the carrier concentration continues to increase as the doping concentration increases. In addition, doping leads to improved crystal structure of n-PT4, and the crystallinity does not decrease significantly with increasing doping concentration; even the carrier mobility increases with it. The synergistic effect of these two leads to both n-PT3 and n-PT4 achieving a breakthrough of 100 in conductivity and power factor. The DMlmC-doped n-PT4 achieves a power factor of over 150 µW m-1 K-2 . These values are among the highest for n-type organic thermoelectric materials.
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Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death. China has the largest population of patients with traumatic spinal cord injury. Previous studies of traumatic spinal cord injury in China have mostly been regional in scope; national-level studies have been rare. To the best of our knowledge, no national-level study of treatment status and economic burden has been performed. This retrospective study aimed to examine the epidemiological and clinical features, treatment status, and economic burden of traumatic spinal cord injury in China at the national level. We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China. Patient epidemiological and clinical features, treatment status, and total and daily costs were recorded. Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program. The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall (annual percentage change, -0.5% and 2.1%, respectively). A total of 10,053 (74.7%) patients underwent surgery. Only 2.8% of patients who underwent surgery did so within 24 hours of injury. A total of 2005 (14.9%) patients were treated with high-dose (≥ 500 mg) methylprednisolone sodium succinate/methylprednisolone (MPSS/MP); 615 (4.6%) received it within 8 hours. The total cost for acute traumatic spinal cord injury decreased over the study period (-4.7%), while daily cost did not significantly change (1.0% increase). Our findings indicate that public health initiatives should aim at improving hospitals' ability to complete early surgery within 24 hours, which is associated with improved sensorimotor recovery, increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.
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Polycystic ovary syndrome (PCOS) is an endocrine disorder, affecting women of child-bearing age, and the incidence rate is growing and assuming epidemic proportions. The etiology of PCOS remains unknown and there is no cure. Some animal models for PCOS have been established which have enhanced our understanding of the underlying mechanisms, but omics data for revealing PCOS pathogenesis and for drug discovery are still lacking. In the present study, proteomics analysis was used to construct a protein profile of the ovaries in a PCOS mouse model. The result showed a clear difference in protein profile between the PCOS and control group, with 495 upregulated proteins and 404 downregulated proteins in the PCOS group. The GO term and KEGG pathway analyses of differentially expressed proteins mainly showed involvement in lipid metabolism, oxidative stress, and immune response, which are consistent with pathological characteristics of PCOS in terms of abnormal metabolism, endocrine disorders, chronic inflammation and imbalance between oxidant and antioxidant levels. Also, we found that inflammatory responses were activated in the PCOS ovarium, while lipid biosynthetic process peroxisome, and bile secretion were inhibited. In addition, we found some alteration in unexpected pathways, such as glyoxylate and dicarboxylate metabolism, which should be investigated. The present study makes an important contribution to the current lack of PCOS ovarian proteomic data and provides an important reference for research and development of effective drugs and treatments for PCOS.
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BACKGROUND Isolated distal deep vein thrombosis (ICMVT) increases the risk of pulmonary embolism. Although predictive models are available, their utility in predicting the risk is unknown. To develop a clinical prediction model for isolated distal calf muscle venous thrombosis, data from 462 patients were used to assess the independent risk variables for ICMVT. MATERIAL AND METHODS The area under curve (AUC) for Model A and Model B were calculated and other risk factors were based on age, pitting edema in the symptomatic leg, calf swelling with least 3 cm larger than the asymptomatic leg, recent bed rest for 3 days or more in the past 4 weeks, requiring general or major surgery with regional anesthesia, sex, and local tenderness distributed along the deep venous system as independent predictors of calf muscle venous thrombosis. Model A includes the risk variables for C-reactive protein and D-dimer. RESULTS The area under ROC curve for Model A training set was 0.924 (95% CI: 0.895-0.952), the area under ROC curve for Model B training set was 0.887 (95% CI: 0.852-0.922), and the AUC difference between the 2 models was statistically significant (P<0.001); the area under ROC curve for Model A obtained in the validation set was 0.902 (95% CI: 0.844-0.961), the area under ROC curve for Model B was 0.842 (95% CI: 0. 0.773-0.910), and the difference between the 2 models was statistically significant (P=0.012). CONCLUSIONS Predictive Model A better predicts isolated calf muscle venous thrombosis and is able to help clinicians rapidly and early diagnose ICMVT, displaying higher utility for missed diagnosis prevention and disease therapy.