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Abdominal aortic aneurysm (AAA) is a degenerative disease that caused mortality in people aged >65. Senescence plays a critical role in AAA pathogenesis. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. Our Previous study found cyclic nucleotide phosphodiesterase 1C (PDE1C) exacerbate AAA through aggravate vascular smooth muscle cells (VSMCs) senescence by downregulating Sirtuin1 (SIRT1) expression and activity. Vinpocetine as a selective inhibitor of PDE1 and a clinical medication for cerebral vasodilation, it is unclear whether vinpocetine can rely on SIRT1 to alleviate AAA. This study showed that pre-treatment with vinpocetine remarkably prevented aneurysmal dilation and reduced aortic rupture in elastase-induced AAA mice. In addition, the elastin degradation, MMP (matrix metalloproteinase) activity, macrophage infiltration, ROS production, collagen fibers remodeling, and VSMCs senescence were decreased in AAA treated with vinpocetine. While these effects were unable to exert in VSMCs-specific SIRT1 knockout AAA mice. Accordingly, we revealed that vinpocetine suppressed migration, proliferation, and senescence in VSMCs. Moreover, vinpocetine reduced SIRT1 degradation by inhibiting lysosome-mediated autophagy. In conclusion, this study indicated that vinpocetine may be as a potential drug for therapy AAA through alleviate VSMCs senescence via the SIRT1-dependent pathway.
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Vehicles generally move smoothly and with high speeds on elevated roads, thereby producing specific traffic-related carbon emissions in contrast to ground roads. Hence, a portable emission measurement system was adopted to determine traffic-related carbon emissions. The on-road measurement results revealed that the instantaneous emissions of CO2 and CO from elevated vehicles were 17.8% and 21.9% higher than those from ground vehicles, respectively. Based on it, the vehicle specific power was confirmed to exhibit a positive exponential relationship with instantaneous CO2 and CO emissions. In addition to carbon emissions, carbon concentrations on roads were simultaneously measured. The average CO2 and CO emissions on elevated roads in urban areas were 1.2% and 6.9% higher than those on ground roads, individually. Finally, a numerical simulation was performed, and the results verified that elevated roads could deteriorate the air quality on ground roads but improve the air quality above them. What ought to be paid attention to is that the elevated roads present varied traffic behaviour and cause particular carbon emissions, indicating that comprehensive consideration and further balance among the traffic-related carbon emissions are necessary when building elevated roads to alleviate the traffic congestion in urban areas.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Emissões de Veículos/análise , Monitoramento Ambiental/métodos , Carbono/análise , Dióxido de Carbono/análise , Poluição do Ar/análiseRESUMO
BACKGROUND: To evaluate the value of ultrasound-guided vacuum-assisted excision (US-guided VAE) in the treatment of intraductal papillomas, including intraductal papillomas with atypical ductal hyperplasia (ADH), and to evaluate the lesion characteristic features affecting the local recurrence rate. MATERIALS AND METHODS: Between August 2011 and December 2020, 91 lesions of 91 patients underwent US-guided VAE and were diagnosed with intraductal papilloma with or without ADH. The recurrence rate of intraductal papilloma was evaluated on follow-up US. The lesion characteristic features were analyzed to identify the factors affecting the local recurrence rate. RESULTS: The local recurrence rate of intraductal papillomas removed by US-guided VAE was 7.7% (7/91), with the follow-up duration 12-92 months (37.4 ± 23.9 months). Of the 91 patients, five cases diagnosed as intraductal papilloma with ADH did not recur, with the follow-up time 12-47 months (26.4 ± 14.4 months). There were no malignant transformation in all 91 cases during the follow-up period. All 7 patients recurred 7-58 months (22.8 ± 19.2 months) after US-guided VAE. There were no significant differences between the non-recurrence and recurrence groups in terms of age, side, distance from nipple, lesion size, BI-RADS category, with ADH, or history of excision (p > 0.05). CONCLUSIONS: US-guided VAE is an effective method for the treatment of intraductal papilloma, including intraductal papilloma with ADH. It avoids invasive surgical excision, but regular follow-up is recommended to prevent recurrence or new onset due to multifocality. Any suspicious lesions during the follow-up should be actively treated.
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Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Papiloma Intraductal , Humanos , Feminino , Papiloma Intraductal/diagnóstico por imagem , Papiloma Intraductal/cirurgia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Ultrassonografia , Biópsia por Agulha , Ultrassonografia de Intervenção , Estudos RetrospectivosRESUMO
PURPOSE: The aim of this study was to analyze the role of ultrasound-guided vacuum-assisted excision (US-guided VAE) in the treatment of high-risk breast lesions and to evaluate the clinical and US features of the patients associated with recurrence or development of malignancy. MATERIALS AND METHODS: Between April 2010 and September 2021, 73 lesions of 73 patients underwent US-guided VAE and were diagnosed with high-risk breast lesions. The incidence of recurrence or development of malignancy for high-risk breast lesions was evaluated at follow-up period. The clinical and US features of the patients were analyzed to identify the factors affecting the recurrence or development of malignancy rate. RESULTS: Only benign phyllodes tumors on US-guided VAE showed recurrences, while other high-risk breast lesions that were atypical ductal hyperplasia (ADH), lobular neoplasia (atypical lobular hyperplasia/lobular carcinoma in situ), radial scar, and flat epithelial atypia did not show recurrences or malignant transformation. The recurrence rate of the benign phyllodes tumor was 20.8% (5/24) in a mean follow-up period of 34.3 months. The recurrence rate of benign phyllodes tumor with distance from nipple of less than 1 cm was significantly higher than that of lesions with distance from nipple of more than 1 cm (75% vs. 10%, p < 0.05). CONCLUSIONS: Benign phyllodes tumors without concurrent breast cancer could be safely followed up instead of surgical excision after US-guided VAE when the lesions were classified as BI-RADS 3 or 4A by US.
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Neoplasias da Mama , Carcinoma in Situ , Tumor Filoide , Humanos , Feminino , Tumor Filoide/diagnóstico por imagem , Tumor Filoide/cirurgia , Tumor Filoide/patologia , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Ultrassonografia , Mamilos/patologia , Hiperplasia , Carcinoma in Situ/patologia , Ultrassonografia de Intervenção , Estudos RetrospectivosRESUMO
Vitamin D can not only regulate calcium and phosphorus metabolism, but also exert an immunoregulatory effect. Vitamin D deficiency is common in patients with Crohn's disease (CD). Studies have shown that vitamin D is associated with CD and other autoimmune diseases and can improve the condition of patients with CD and promote their recovery by regulating intestinal immunity, repairing the intestinal mucosal barrier, inhibiting intestinal fibrosis, enhancing the response to infliximab, and regulating intestinal microbiota. Exogenous vitamin D supplementation can induce disease remission while increasing the serum level of vitamin D. However, only a few randomized, double-blind, and placebo-controlled trials have investigated the therapeutic effect of vitamin D in CD, and the optimal form of vitamin D supplementation, the specific dosage of vitamin D supplementation, and the optimal serum maintenance concentration of vitamin D remain to be clarified. This article mainly discusses the mechanism of action of vitamin D in CD and the beneficial effect of exogenous vitamin D supplementation on CD.
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Doença de Crohn , Vitamina D , Humanos , Cálcio da Dieta , Doença de Crohn/tratamento farmacológico , Suplementos Nutricionais , Infliximab , Vitamina D/farmacologia , Vitamina D/uso terapêuticoRESUMO
OBJECTIVES: To investigate the nutritional status and its influencing factors in children with newly diagnosed inflammatory bowel disease (IBD). METHODS: A retrospective analysis was conducted on the clinical data of children who were diagnosed with IBD for the first time in Hunan Children's Hospital from January 2015 to December 2021. Diagnostic delay was defined as the time from the symptom onset to IBD diagnosis being in the upper quartile (P76-P100) of all IBD children in the study. Multivariate logistic regression analysis was used to explore the risk factors for emaciation and growth retardation. RESULTS: A total of 125 children with newly diagnosed IBD were included, with Crohn's disease being the main type (91.2%). The rates of emaciation and growth retardation were 42.4% (53 cases) and 7.2% (9 cases), respectively, and the rate of anemia was 77.6% (97 cases). Diagnostic delay was noted in 31 children (24.8%), with the time from the symptom onset to IBD diagnosis of 366 to 7 211 days. Multivariate logistic regression analysis showed that diagnostic delay was a risk factor for emaciation and growth retardation (OR=2.73 and OR=4.42, respectively; P<0.05) and that age was positively associated with emaciation (OR=1.30, P<0.05). CONCLUSIONS: Children with newly diagnosed IBD have poor nutritional status, and the rates of anemia, emaciation, and growth retardation are high. Diagnostic delay is associated with malnutrition in children with IBD.
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Colite Ulcerativa , Doenças Inflamatórias Intestinais , Desnutrição , Humanos , Criança , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Estado Nutricional , Estudos Retrospectivos , Emaciação/complicações , Diagnóstico Tardio , Doenças Inflamatórias Intestinais/complicações , Desnutrição/complicações , Transtornos do Crescimento/complicaçõesRESUMO
Cardiovascular disease is a common comorbidity in patients with cancer, and the main leading cause of noncancer-related deaths in cancer survivors. Considering that current antitumor drugs usually induce cardiovascular injury, the quest for developing new antitumor drugs, especially those with cardiovascular protection, is crucial for improving cancer prognosis. MK2206 is a phase II clinical anticancer drug and the role of this drug in cardiovascular disease is still unclear. Here, we revealed that MK2206 significantly reduced vascular inflammation, atherosclerotic lesions, and inhibited proliferation of vascular smooth muscle cell in ApoE-/- mice in vivo. We demonstrated that MK2206 reduced lipid accumulation by promoting cholesterol efflux but did not affect lipid uptake and decreased inflammatory response by modulating inflammation-related mRNA stability in macrophages. In addition, we revealed that MK2206 suppressed migration, proliferation, and inflammation in vascular smooth muscle cells. Moreover, MK2206 inhibited proliferation and inflammation of endothelial cells. The present results suggest that MK2206, as a promising drug in clinical antitumor therapy, exhibits anti-inflammatory and antiatherosclerotic potential. This report provides a novel strategy for the prevention of cardiovascular comorbidities in cancer survivors.
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Aterosclerose , Células Endoteliais , Animais , Apolipoproteínas E/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Movimento Celular , Proliferação de Células , Colesterol/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Compostos Heterocíclicos com 3 Anéis , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismoRESUMO
Following the outbreak of the COVID-19 pandemic, various lockdown strategies restrained global economic growth bringing a significant decline in maritime transportation. However, the previous studies have not adequately recognized the specific impacts of COVID-19 on maritime transportation. In this study, a series of analyses of the Baltic Dry Index (BDI), the China Coastal Bulk Freight Index (CCBFI) and of container throughputs with and without the impact of COVID-19 were carried out to assess changing trends in dry bulk and container transportation. The results show that global dry bulk transportation was largely affected by lockdown policies in the second month during COVID-19, and BDI presented a year-on-year decrease of approximately 35.5% from 2019 to 2020. The CCBFI showed an upward trend in the second month during COVID-19, one month ahead of the BDI. The container throughputs at Shanghai Port, the Ports of Hong Kong, the Ports of Singapore and the Ports of Los Angeles from 2019 to 2020 presented the largest year-on-year drops of approximately 19.6%, 7.1%, 10.6% and 30.9%, respectively. In addition, the authors developed exponential smoothing models of BDI, CCBFI, and container transportation, and calculated the percentage prediction error between the observed and predicted values to examine the impact of exogenous effects on the shipping industry due to the outbreak of COVID-19. The results are consistent with the conclusions obtained from the comparison of BDI, CCBFI, and container transportation during the same period in 2020 and 2019. Finally, on the basis of the findings, smart shipping and special support policies are proposed to reduce the negative impacts of COVID-19.
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Chronic obstructive pulmonary disease (COPD) is a common and frequently-occurring disease in the department of respiratory medicine,the pathogenesis of which involves both environmental factors and genetic factors.In recent years,with the application of new methods such as genome-wide association study,researchers have discovered a large number of gene mutations associated with lung function and COPD,providing a new perspective on the pathogenesis of COPD and potential therapeutic targets.This article reviews the research achievements and application progress of genomics in COPD.
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Estudo de Associação Genômica Ampla , Doença Pulmonar Obstrutiva Crônica , Estudo de Associação Genômica Ampla/métodos , Genômica , Humanos , Doença Pulmonar Obstrutiva Crônica/genéticaRESUMO
OBJECTIVES: To study the clinical features of intestinal polyps and the risk factors for secondary intussusception in children. METHODS: A retrospective analysis was performed for the medical data of 2 669 children with intestinal polyps. According to the presence or absence of secondary intussusception, they were divided into two groups: intussusception (n=346) and non-intussusception (n=2 323). Related medical data were compared between the two groups. The multivariate logistic regression analysis was used to identify the risk factors for secondary intussusception. RESULTS: Among the children with intestinal polyps, 62.42% were preschool children, and the male/female ratio was 2.08â¶1; 92.66% had hematochezia as disease onset, and 94.34% had left colonic polyps and rectal polyps. There were 346 cases of secondary intussusception, with an incidence rate of 12.96% (346/2 669). Large polyps (OR=1.644, P<0.001), multiple polyps (≥2) (OR=6.034, P<0.001), and lobulated polyps (OR=93.801, P<0.001) were the risk factors for secondary intussusception. CONCLUSIONS: Intestinal polyps in children often occur in preschool age, mostly in boys, and most of the children have hematochezia as disease onset, with the predilection sites of the left colon and the rectum. Larger polyps, multiple polyps, and lobulated polyps may increase the risk of secondary intussusception, and endoscopic intervention is needed as early as possible to improve prognosis.
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Intussuscepção , Pré-Escolar , Feminino , Hemorragia Gastrointestinal , Humanos , Pólipos Intestinais/complicações , Intussuscepção/complicações , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To investigate the incidence rates of Clostridium difficile colonization and Clostridium difficile infection (CDI) in children with inflammatory bowel disease (IBD) and the susceptibility factors for CDI in children with IBD. METHODS: A total of 62 children diagnosed with IBD were enrolled as the IBD group. Forty-two children who attended the hospital due to persistent or chronic diarrhea and were excluded from IBD were enrolled as the non-IBD group. The incidence rate of CDI was compared between the two groups. According to the presence or absence of CDI, the IBD group was subdivided into two groups:IBD+CDI (n=12) and non-CDI IBD (n=50), and the clinical data were collected from the two groups to analyze the susceptibility factors for CDI. RESULTS: The IBD group had a significantly higher incidence rate of CDI[19% (12/62) vs 2% (1/42); P < 0.05] than the non-IBD group (P < 0.05). Compared with the non-CDI IBD group, the IBD+CDI group had a significantly longer disease course (P < 0.05), and a significantly higher proportion of children with fever, diarrhea, or abdominal pain (P < 0.05). The IBD+CDI group had significantly higher activity indices of pediatric Crohn's disease, C-reactive protein levels and erythrocyte sedimentation rate than the non-CDI IBD group (P < 0.05). The univariate analysis showed that compared with the non-CDI IBD group, the IBD+CDI group had a significantly higher proportion of children with moderate-to-severe disease, use of glucocorticoids, or treatment with broad-spectrum antibiotics for more than 14 days before diagnosis (P < 0.05). CONCLUSIONS: The children with IBD have a higher incidence of CDI than those without IBD. Severe disease conditions and use of broad-spectrum antibiotics or glucocorticoids may be associated with an increased incidence of CDI in children with IBD.
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Clostridioides difficile , Infecções por Clostridium , Doença de Crohn , Doenças Inflamatórias Intestinais , Criança , Infecções por Clostridium/epidemiologia , Humanos , Incidência , Doenças Inflamatórias Intestinais/complicaçõesRESUMO
BACKGROUND: Chronic brain hypoperfusion (CBH) is closely related to Alzheimer's disease (AD) and vascular dementia (VaD). Meanwhile, synaptic pathology plays a prominent role in the initial stage of AD and VaD. However, whether and how CBH impairs presynaptic plasticity is currently unclear. METHODS: In the present study, we performed a battery of techniques, including primary neuronal culture, patch clamp, stereotaxic injection of the lentiviral vectors, morris water maze (MWM), dual luciferase reporter assay, FM1-43 fluorescence dye evaluation, qRT-PCR and western blot, to investigate the regulatory effect of miR-153 on hippocampal synaptic vesicle release both in vivo and in vitro. The CBH rat model was generated by bilateral common carotid artery ligation (2VO). RESULTS: Compared to sham rats, 2VO rats presented decreased field excitatory postsynaptic potential (fEPSP) amplitude and increased paired-pulse ratios (PPRs) in the CA3-CA1 pathway, as well as significantly decreased expression of multiple vesicle fusion-related proteins, including SNAP-25, VAMP-2, syntaxin-1A and synaptotagmin-1, in the hippocampi. The levels of microRNA-153 (miR-153) were upregulated in the hippocampi of rats following 2VO surgery, and in the plasma of dementia patients. The expression of the vesicle fusion-related proteins affected by 2VO was inhibited by miR-153, elevated by miR-153 inhibition, and unchanged by binding-site mutation or miR masks. FM1-43 fluorescence images showed that miR-153 blunted vesicle exocytosis, but this effect was prevented by either 2'-O-methyl antisense oligoribonucleotides to miR-153 (AMO-153) and miR-masking of the miR-153 binding site in the 3' untranslated region (3'UTR) of the Snap25, Vamp2, Stx1a and Syt1 genes. Overexpression of miR-153 by lentiviral vector-mediated miR-153 mimics (lenti-pre-miR-153) decreased the fEPSP amplitude and elevated the PPR in the rat hippocampus, whereas overexpression of the antisense molecule (lenti-AMO-153) reversed these changes triggered by 2VO. Furthermore, lenti-AMO-153 attenuated the cognitive decline of 2VO rats. CONCLUSIONS: Overexpression of miR-153 controls CBH-induced presynaptic vesicle release impairment by posttranscriptionally regulating the expression of four vesicle release-related proteins by targeting the 3'UTRs of the Stx1a, Snap25, Vamp2 and Syt1 genes. These findings identify a novel mechanism of presynaptic plasticity impairment during CBH, which may be a new drug target for prevention or treatment of AD and VaD. Video Abstract.
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Demência Vascular/metabolismo , Hipóxia-Isquemia Encefálica/metabolismo , MicroRNAs/fisiologia , Vesículas Sinápticas/metabolismo , Idoso , Animais , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Proteína 25 Associada a Sinaptossoma/metabolismo , Sinaptotagmina I/metabolismo , Sintaxina 1/metabolismo , Proteína 2 Associada à Membrana da Vesícula/metabolismoRESUMO
Under the hydrothermal reaction condition, we prepared a new 3D Eu(III)-based coordination polymer (CP) [Eu(H2-DHBDC)0.5(DHBDC)0.5 (H2O)2] n ·H2O (1, H4-DHBDC = 2,5-dihydroxy-1,4-terephthalic acid). Furthermore, we assessed the inhibitory influence on cervical cancer cells of this compound. First, for testing the anti-viability of the compound against cervical cancer cells, the cell counting kit-8 (CCK-8) assay was carried out. Then, reactive oxygen species (ROS) detection kit was used to determine the ROS accumulation in the cervical cancer cells. Finally, after the Annexin V-FITC/PI apoptosis assay was finished, it was used for apoptotic cervical cancer cells after treated with compound. From the results of the software of pose scoring and molecular docking, we can see that the compound may bind to p91 by the functional side-chain of the ligand, which provided potential regulatory mechanisms for the compound.
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Polímeros/química , Espécies Reativas de Oxigênio/química , Neoplasias do Colo do Útero , Apoptose , Feminino , Humanos , Simulação de Acoplamento MolecularRESUMO
BACKGROUND: In China, traditional preoperative planning of unilateral breast reconstruction mainly depends on anthropometric measurement and visual assessment. Thus, the lack of objective assessment of breast volume and shape would likely result in suboptimal reconstruction outcomes. Three-dimensional surface imaging (3D-SI), which could provide objective measurement data of the breast, may be a promising solution to this problem. METHODS: A retrospective review of patients undergoing tissue expander (TE)/implant breast reconstruction without any mammoplasty surgery on the contralateral sides in our hospital from August 2013 to May 2018 was performed. All the patients underwent unilateral mastectomy with immediate or delayed insertion of TE, followed by an exchange of a silicone gel implant without contralateral procedures. 3D images were obtained at the time of preoperation, the routine expansion visit, and post-exchange of implant. The breast volume measured by 3D-SI served as a guide to conduct the surgery management, such as in deciding the total volume of expansion and guiding the final implant size selection. 3D-SI also provided objective data to evaluate the final outcomes of the reconstruction. RESULTS: Fifty-one patients were included in this study, in which eighteen patients underwent immediate TE insertion and thirty-three patients underwent delayed TE insertion. The ptosis degree of contralateral breasts was assessed as follows: forty-four were normal, and seven showed mild ptosis. The average expansion degree was controlled at 161.6% ± 14.1% compared to the contralateral breasts. The volume of implants exchanged had a strong linear correlation with the 3D volume of the contralateral breasts at the end of expansion (P < 0.01). The mean time of follow-up was 9.1 ± 6.6 months. There was only one patient who experienced TE leakage with secondary infection and received TE exchange. For the immediate reconstruction group, the overall breast symmetry improved at the completion of implant exchange (P < 0.01), with an average asymmetry of 5.3% ± 4.0% compared with 10.6% ± 6.1% initially. For the delayed reconstruction group, the reconstructed side achieved good volume symmetry to the contralateral side (P > 0.05). There was no significant difference in breast basal width between bilateral breasts post-reconstruction (P > 0.05). CONCLUSION: 3D-SI serves as a valuable adjunct by providing accurate 3D volume of breasts within TE/implant breast reconstruction in Chinese patients without obvious breast ptosis, which could facilitate surgeons to achieve good reconstructive outcomes. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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Implantes de Mama , Neoplasias da Mama , Mamoplastia , China , Humanos , Mastectomia , Estudos Retrospectivos , Dispositivos para Expansão de Tecidos , Resultado do TratamentoRESUMO
The transportation of container trucks in urban areas not only frequently causes traffic jams but also produces severe air pollution. With regard to this consideration, measurements of particle concentrations and traffic volume on different polluted days were carried out to discover the varied characteristics of particles from container truck transportation in the port area. Based on the original data, descriptive statistics were performed firstly to reveal the statistical characteristics of particle number concentrations (PNC). The Kolmogorov-Smirnov test as well as the Anderson-Darling test was adopted to identify the "best-fit" distributions on PNC data while the corresponding maximum likelihood estimation was conducted to estimate the parameters of the identified distribution. Additionally, the Pearson correlation analysis and principal component analysis were performed respectively to reveal the relationships between traffic volume and PNC. The results showed that on a hazy day, PNC levels in the morning were generally higher than those in the afternoon, while on a non-hazy day, the results were opposite. Particles in all sizes on a non-hazy day and larger than 0.5 µm on a hazy day were verified to fit the lognormal distribution. In contrast to the particles below 2 µm, the particles above 2 µm exhibited higher correlations with the traffic flow of a container truck in the morning on a hazy day. These results indicate the importance of reducing air pollution from a container truck and provide policymakers with a foundation for possible measures in a port city.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Cidades , Monitoramento Ambiental , Veículos Automotores , Material Particulado/análise , Emissões de Veículos/análiseRESUMO
OBJECTIVES: The present study aims to identify the genotype-phenotype correlation in children with Peutz-Jeghers Syndrome (PJS) through the analysis of STK11 gene mutations in the context of clinical and pathological characteristics. METHOD: In this observational cohort study, the clinical characteristics of 18 families diagnosed with pediatric PJS were collected. Genomic DNA from the peripheral blood of affected children and their family members was collected. The coding region of STK11 was amplified by PCR and screened for mutation by Sanger sequencing. The families that were negative for STK11 mutation were further assessed by multiplex ligation-dependent probe amplification (MLPA). RESULT: Initial presentation in affected children was at 1.6 to 14.2 years and included anemia in 8 patients whereas 6 presented for screening by virtue of family history. All patients underwent endoscopy, colonoscopy, and polypectomy. Polyps were distributed throughout the gastrointestinal (GI) tract, including the small intestine, stomach, colon, and rectum.In the 18 pediatric PJS families, STK11 mutations were detected in 8 families by Sanger sequencing, and large deletions were detected in 3 by MLPA, respectively. Nine of the 11 STK11 mutations were de novo, 3 were novel (c.419T>C:p.L140P, c.314T>G:p.L105X), and (c.488_489insACGG p.L164fs). CONCLUSIONS: Although the main clinical features of pediatric PJS were similar to those of PJS cases in adults, a high frequency of STK11 de novo mutations were encountered in our population of patients with PJS.
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Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinases/genética , Quinases Proteína-Quinases Ativadas por AMP , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Reação em Cadeia da Polimerase Multiplex , Mutação , Linhagem , Análise de Sequência de DNA , Deleção de SequênciaRESUMO
OBJECTIVE: To construct the recombinant adenoviral vector carrying the rat interleukin-10 (rIL-10) gene, and to investigate whether it is stably expressed in bone marrow mesenchymal stem cells. METHODS: The rIL-10 gene was amplified by PCR from template rIL-10 cDNA, and the recovered 656 bp rIL-10 DNA fragment was cloned into pcDNA3.1 to construct pcDNA3.1-IL-10. Then HEK293 cells were transfected with pcDNA3.1-IL-10 and adenoviral vector for homologous recombination, and sequencing and PCR were used to evaluate whether recombination was successful. HEK293 cells were lysed by repeated freeze-thaw cycles, and bone marrow mesenchymal stem cells were infected with the virus solution containing the rIL-10 gene. Western blot was used to measure the expression of rIL-10 in bone marrow mesenchymal stem cells. RESULTS: Sequencing and PCR verified that the rIL-10 adenoviral vector was successfully constructed, with a virus titer of 4×109â PFU/mL. The expression of IL-10 was detected after bone marrow mesenchymal stem cells were infected by the virus solution containing the rIL-10 gene. CONCLUSIONS: The constructed rIL-10 recombinant adenovirus can mediate the stable expression of rIL-10 gene in bone marrow mesenchymal stem cells, which provides a basis for gene transplantation therapy of inflammatory bowel disease.
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Células-Tronco Mesenquimais , Adenoviridae , Animais , Células da Medula Óssea , Vetores Genéticos , Células HEK293 , Humanos , Interleucina-10 , Ratos , TransfecçãoRESUMO
OBJECTIVE: To study the effect of glutamine-supplemented enteral nutrition in regulating the apoptosis of intestinal mucosal cells and promoting mucosal healing in young rats with inflammatory bowl disease (IBD). METHODS: A total of 80 male Sprague-Dawley rats aged 4-5 weeks were randomly divided into 4 groups: blank control, IBD model, short peptide, and short peptide+glutamine (n=20 each). The IBD model was prepared by a single colon perfusion of 3-nitrobenzene sulfonic acid. At 3 days after modeling, the rats in the short peptide group were fed with short peptide formula (100â mL/kg), and those in the short peptide+glutamine group were fed with short peptide formula (100 mL/kg) and glutamine (0.5â g/kg). The course of intervention was 1 week. General conditions were observed after the experiment and their intestinal mucosal tissue was obtained. Hematoxylin-eosin staining was used to observe the pathological change of the intestinal mucosa. RT-PCR was used to measure the expression of apoptosis-regulating genes (bax and bc1-2) and apoptotic signal transduction factors (Caspase-3 and Caspase-9) in the intestinal mucosa. Western blot was used to measure the expression of insulin-like growth factor-1 (IGF-1) in the colonic mucosa. RESULTS: The IBD model group had poorer general conditions than the other three groups (blank control, short peptide and short peptide+glutamine), and the short peptide+glutamine group had better general conditions than the IBD model and short peptide groups. The IBD model group had significantly higher mRNA expression of bax than the other three groups (P<0.05). There was no significant difference in the mRNA expression of bcl-2, Caspase-3 and Caspase-9 among the 4 groups (P>0.05). The short peptide group had a significantly higher level of IGF-1 than the short peptide+glutamine, blank control and IBD model groups (P<0.05). CONCLUSIONS: Glutamine-supplemented enteral nutrition can effectively improve the general nutritional status of young rats with IBD, but it is not better than exclusive enteral nutrition in inhibiting the apoptosis of colonic mucosal cells and stimulating the synthesis of IGF-1 in the intestinal mucosa.
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Nutrição Enteral , Animais , Apoptose , Glutamina , Mucosa Intestinal , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUNDS/AIMS: It has been reported that myocardial infarction (MI) is a risk factor for vascular dementia. However, the molecular mechanism remains largely unknown. METHODS: MI mice were generated by ligation of the left coronary artery (LCA) for 4 weeks. Passive and active avoidance tests were performed to evaluate the cognitive ability of MI mice. A theta-burst stimulation (TBS) protocol was applied to elicit long-term potentiation (LTP) of the perforant pathway-dentate gyrus synapse (PP-DG). Western blot analysis was employed to assess protein levels. RESULTS: In this study, we demonstrated that after 4 weeks of MI, C57BL/6 mice had significantly impaired memory. Compared with the sham group, in vivo physiological recording in the MI group revealed significantly decreased amplitude of population spikes (PS) with no effect on the latency and duration of the stimulus-response curve. The amplitude of LTP was markedly decreased in the MI group compared with the sham group. Further examination showed that the expression of the TBS-LTP-related proteins BDNF, GluA1 and phosphorylated GluA1 were all decreased in the MI group compared with those in the sham group. Strikingly, all these changes were prevented by hippocampal stereotaxic injection of an anti-miR-1 oligonucleotide fragment carried by a lentivirus vector (lenti-pre-AMO-1). CONCLUSION: MI induced cognitive decline and TBS-LTP impairment, and decreased BDNF and GluA1 phosphorylation levels from overexpression of miR-1ated were involved in this process.
Assuntos
Potenciação de Longa Duração/fisiologia , MicroRNAs/metabolismo , Infarto do Miocárdio/patologia , Animais , Antagomirs/metabolismo , Comportamento Animal , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células Cultivadas , Giro Denteado/fisiologia , Modelos Animais de Doenças , Estimulação Elétrica , Eletrodos Implantados , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Infarto do Miocárdio/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Mapas de Interação de Proteínas , Receptores de AMPA/metabolismo , Sinapses/metabolismoRESUMO
A total of two hundred cases of surface Fourier transform infrared (FTIR) spectra from normal female breast were obtained by scanning two hundred enrolled healthy volunteers' upper limit of the right breast outside the skin with two mid-infrared optical fibers and an attenuated total reflectance (ATR) probe. Twelve characteristic bands of the above FTIR spectra, related to deoxyribonucleic acid, ribonucleic acid, proteins, lipids and carbohydrate were analyzed. Thirty-six spectral parameters of these characteristic bands, including peak positions (P), intensities (I) and full width at half maximum (F) of FTIR spectrums, were statistically analyzed. Meantime, 90% normal reference value range, mean value, standard deviation of above characteristic parameters was obtained and calculated. In present study, we had establish the normal reference range of spectral parameters of characteristic bands in the surface Fourier transform infrared spectra scanned from normal female breast, for the first time. Meanwhile, for further implementation of Fourier transform infrared spectroscopy technique in noninvasive, fast and efficient characteristic clinical diagnosis of breast benign and malignant diseases, these research results was of great importance. Eventually, this study also had made an attempt to explore the profound theoretical basis in the biomedical application of Fourier transform infrared spectroscopy technique.