RESUMO
Objective: To investigate the incidence and predictors of 90-day poor clinical outcome after successful endovascular treatment for acute basilar artery occlusion. Methods: Patients were selected from the Acute Ischemic Stroke Cooperation Group of Endovascular Treatment (ANGEL) registry, which was a prospective, multicenter registry study between June 2015 and December 2017. The demographic characteristics, past history, personal history, vital signs, National Institutes of Health Stroke Scale (NIHSS) score, imaging examination, onset/admission/puncture/end of operation, operation-related variables, medication during operation, patency of occluded blood vessels after operation, etiology classification, and 90-day modified Rankin scale (mRS) score were collected. Successful endovascular treatment was defined as modified thrombolysis in cerebral infarction (mTICI) 2b-3. Poor outcome was defined as 90-day mRS 4-6. Multivariate logistic regression analysis was performed to analyze the predictors of poor clinical outcome after successful endovascular treatment. Results: A total of 170 (128 males and 42 females) acute basilar artery occlusion patients undergoing successful endovascular treatment were included in the analysis, with the median age of [M (Q1, Q3)] of 64 (55, 70) years. Poor clinical outcome occurred in 72 patients (42.4%). Multivariate logistic regression analysis revealed that high baseline NIHSS score (OR=1.166, 95%CI: 1.109-1.225, P<0.001) and high baseline systolic blood pressure (OR=1.032, 95%CI: 1.010-1.053, P=0.003) were the independent predictors of poor clinical outcome. Conclusions: The incidence of 90-day poor clinical outcome after successful endovascular treatment for acute basilar artery occlusion is 42.4%. High baseline NIHSS score and systolic blood pressure are associated with the poor clinical outcome.
Assuntos
Arteriopatias Oclusivas , Procedimentos Endovasculares , AVC Isquêmico , Feminino , Humanos , Masculino , Arteriopatias Oclusivas/cirurgia , Artéria Basilar/cirurgia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Incidência , AVC Isquêmico/complicações , Estudos Prospectivos , Trombectomia/efeitos adversos , Trombectomia/métodos , Resultado do Tratamento , Pessoa de Meia-Idade , IdosoRESUMO
To evaluate the urate-lowering effect and potential drug targets of antihypertensive agent allisartan isoproxil (ALI) and its bioactive metabolite EXP3174, we developed an acute hyperuricemic zebrafish model using potassium oxonate and xanthine sodium salt. Losartan potassium served as the positive control (reference drug). In this model, ALI and losartan potassium exerted a greater urate-lowering effect than EXP3174 indicating that the latter is not the critical substance for elimination of uric acid. The quantitative real-time PCR showed that ALI upregulates the expression of intestinal urate transporters genes ABCG2, PDZK1, and SLC2A9 (p<0.01). Thus, we can suggest that this substance promotes uric acid excretion mainly by interacting with intestinal urate transporters.
Assuntos
Hiperuricemia , Losartan , Animais , Losartan/farmacologia , Losartan/metabolismo , Ácido Úrico/metabolismo , Peixe-Zebra/metabolismo , Rim/metabolismo , Hiperuricemia/tratamento farmacológico , Hiperuricemia/genética , Hiperuricemia/metabolismoRESUMO
Objective: To analyze the level of chromosome aberration in lymphocytes of medical radiation workers and its influencing factors. Methods: From July to September 2020, 252 medical workers in a tertiary hospital were selected as the study subjects and 107 preserviceworkers were selected as the control group. The Chromosomal aberrations of peripheral blood lymphocytes were measured using conventional cytogenetic analysis method, and the differences were analyzed. Results: The frequencies of dicentric puls centric ring, total chromosome-type aberrations, and abnormal detection rate in the radiation group were significantly higher than those in the control group (Z=2.59, 3.74, 9.99, P<0.05). There was significant difference in the frequencies of dicentric plus centric ring and total chromosome-type aberrations among different types of work (χ(2)=8.59, 8.17, 11.39, P<0.05), and the frequencies of dicentric plus centric ring were significantly higher in the interventional radiology group than those in diagnostic radiology (χ(2)=2.90, P<0.05), While the rates of acentric fragment and total chromosome-type aberrations were significantly higher in the nuclear medicine group than those in diagnostic radiology (χ(2)=2.81, 3.19, P<0.05). The difference in the abnormal detection rate of chromosome aberrations between different types of work was statistically significant (P<0.05), and the rate in the interventional radiology group was significantly higher than that in the diagnostic radiology group (χ(2)=7.66, P<0.05). There was no significant difference in chromosome aberration level and abnormal detection rate among different working ages (P>0.05). Poisson regression analysis indicated that the type of work is a risk factor for chromosomal aberration [IRR=2.31 (nuclear medicine group), 1.66 (Radiation therapy), and 1.78 (interventional group) ; P<0.05]. Conclusion: Ionizing radiation causes certain radiation damage to medical radiology workers, and the frequencies of chromosome aberration in the radiation workers of nuclear medicine and interventional radiology groups are relatively high, so radiation protection should be strengthened to ensure the health of relevant workers.
Assuntos
Aberrações Cromossômicas , Radiologia , Humanos , Centros de Atenção Terciária , Grupos Controle , LinfócitosRESUMO
Objective: To systematically study the anti-fibrotic effect of N-acetyl-seryl-as partyl-lysyl-proline (Ac-SDKP) on pulmonary fibrosis. Methods: In May 2021, a computer search was performed on CNKI, Wanfang Knowledge Service Platform, VIP.com, China Biomedical Literature Database, Pubmed, OVID and other databases. The retrieval time was from January 2008 to May 2021. Randomized controlled experiments on the inhibition of pulmonary fibrosis by Ac-SDKP were screened. The control group was the pulmonary fibrosis model group and the experimental group was the Ac-SDKP treatment group. The quality of the literature was assessed using the syrcle risk of bias assessment tool, and data were extracted. Data analysis was Performed using revman 5.4 software. Results: 18 papers were included, with a total of 428 animal models. The results of meta analysis showed that the contents of α-smooth muscle actin (α-SMA), type I collagen, type â ¢ collagen, transforming growth factor-ß (TGF-ß) and Nodule area in the exPerimental group were lower than those in the control grouP. [SMD=-2.44, 95%CI (-3.71--1.17), P=0.000][SMD=-5.36, 95%CI (-7.13--3.59), P=0.000] [SMD=-3.07, 95%CI (-4.13--2.02), P<0.000][SMD=-2.88, 95%CI (-3.63--2.14), P=0.000] [SMD=-1.80, 95%CI (-2.42--1.18), P=0.000], the content of hydroxy proline in the experimental group was higher than that in the control group [SMD=7.62, 95%CI (4.90-10.33), P=0.000], all indexes included in the literature were statistically significant. Conclusion: Ac-SDKP has obvious inhibitory effect on the process of pulmonary fibrosis, and may become a new clinical drug for the treatment of pulmonary fibrosis.
Assuntos
Fibrose Pulmonar , Ratos , Animais , Ratos Wistar , Fibrose , Modelos Animais de Doenças , ProlinaRESUMO
Objective: To study the effect of anti-fibrotic tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on phosphorylated heat shock protein 27 (P-HSP27) and zinc finger family transcriptional repressor 1 (SNAI1) expression to explore the anti-silicosis fibrosis effect of Ac-SDKP. Methods: In December 2014, the rat silicosis animal model was prepared by one-time bronchial infusion of silicon dioxide (SiO(2)) dust. 80 SPF healthy adult Wistar rats were selected, and the rats were divided into 8 groups according to the random number table method, 10 in each group. Model control group for 4 weeks (feeding for 4 weeks) , model control group for 8 weeks (feeding for 8 weeks) : bronchial perfusion with normal saline 1.0 ml per animal. Silicosis model group for 4 weeks (feeding for 4 weeks) and silicosis model group for 8 weeks (feeding for 8 weeks) : bronchial perfusion of 50 mg/ml SiO(2) suspension 1.0 ml per animal. Ac-SDKP administration group for 4 weeks (feeding for 4 weeks) , Ac-SDKP administration group for 8 weeks (feeding for 8 weeks) : Ac-SDKP 800 µg·kg(-1)·d(-1) was administered by intraperitoneal pump. Ac-SDKP preventive treatment group: 48 h after Ac-SDKP 800 µg·kg(-1)·d(-1) administration, bronchial perfusion of SiO(2) suspension 1.0 ml per animal, raised for 8 weeks. Ac-SDKP anti-fibrosis treatment group: after bronchial perfusion of 1.0 ml of SiO(2) suspension for 4 weeks, Ac-SDKP 800 µg·kg(-1)·d(-1) was administered for 4 weeks. Western blotting was used to detect the expression of P-HSP27, SNAI1, α-smooth muscle actin (α-SMA) , and collage typeâ and â ¢ in each group. The expression of P-HSP27 and SNAI1 was detected by immunohistochemistry, and the co-localized expression of P-HSP27 and α-SMA was detected by laser confocal microscopy. Results: Compared with the model control group, the expressions of P-HSP27, SNAI1, α-SMA, and collage typeâ and â ¢ in the silicosis fibrosis area of the rats in the silicosis model group were enhanced, and the differences were statistically significant (P<0.05) . After Ac-SDKP intervention, compared with silicosis model group for 8 weeks, the expressions of P-HSP27, SNAI1 α-SMA, and collage typeâ and â ¢ in the Ac-SDKP preventive and anti-fibrosis treatment groups were significantly decreased, and the differences were statistically significant (P<0.05) . However, the expressions of P-HSP27 SNAI1, and collage typeâ and â ¢ between the Ac-SDKP administration group and the model control group did not change significantly, and the differences were not statistically significant (P>0.05) . Laser confocal results showed that the positive cells expressing P-HSP27 and α-SMA in the lung tissue of the silicosis model group were more than those in the model control group. Compared with the silicosis model group, the Ac-SDKP prevention and anti-fibrosis treatment groups expressing the positive cells of P-HSP27 and α-SMA decreased. Compared with the model control group for 8 weeks, there were some double-positive cells expressing P-HSP27 and α-SMA in the nodules of the silicosis model group for 8 weeks. Conclusion: Ac-SDKP may play an anti-silicic fibrosis effect by regulating the P-HSP27/SNAI1 pathway.
Assuntos
Proteínas de Choque Térmico HSP27 , Silicose , Animais , Oligopeptídeos , Ratos , Ratos Wistar , Dióxido de Silício , Silicose/metabolismoRESUMO
BACKGROUND: Accumulating evidence have shown that the intestinal microbiota plays an important role in prevention of host obesity and metabolism disorders. Recent studies also demonstrate that early life is the key time for the colonization of intestinal microbes in host. However, there are few studies focusing on possible association between intestinal microbiota in the early life and metabolism in adulthood. Therefore the present study was conducted to examine whether the short term antibiotic and/or probiotic exposure in early life could affect intestinal microbes and their possible long term effects on host metabolism. RESULTS: A high-fat diet resulted in glucose and lipid metabolism disorders with higher levels of visceral fat rate, insulin-resistance indices, and leptin. Exposure to ceftriaxone in early life aggravated the negative influences of a high-fat diet on mouse physiology. Orally fed TMC3115 protected mice, especially those who had received treatment throughout the whole study, from damage due to a high-fat diet, such as increases in levels of fasting blood glucose and serum levels of insulin, leptin, and IR indices. Exposure to ceftriaxone during the first 2 weeks of life was linked to dysbiosis of the fecal microbiota with a significant decrease in the species richness and diversity. However, the influence of orally fed ceftriaxone on the fecal microbiota was limited to 12 weeks after the termination of treatment. Of note, at week 12 there were still some differences in the composition of intestinal microbiota between mice provided with high fat diet and antibiotic exposure and those only fed a high fat diet. CONCLUSIONS: These results indicated that exposure to antibiotics, such as ceftriaxone, in early life may aggravate the negative influences of a high-fat diet on the physiology of the host animal. These results also suggest that the crosstalk between the host and their intestinal microbiota in early life may be more important than that in adulthood, even though the same intestinal microbes are present in adulthood.
Assuntos
Dieta Hiperlipídica , Disbiose/complicações , Microbioma Gastrointestinal , Doenças Metabólicas/etiologia , Doenças Metabólicas/microbiologia , Animais , Biodiversidade , Dieta Hiperlipídica/efeitos adversos , Disbiose/microbiologia , Camundongos , Obesidade/etiologia , Obesidade/microbiologiaRESUMO
OBJECTIVE: DNA damage induced by ROS is considered one of the main causes of nucleus pulposus (NP) cells degeneration during the progression of intervertebral disc degeneration (IVDD). cGAS-STING pathway acts as DNA-sensing mechanism for monitoring DNA damage. Recent studies have proved that cGAS-STING contributes to the development of various diseases by inducing inflammation, senescence, and apoptosis. This work explored the role of STING, the main effector of cGAS-STING signaling pathway, in NP degeneration. METHOD: Immunohistochemistry was conducted to measure STING protein levels in the nucleus pulposus tissues from human and puncture-induced IVDD rat models. TBHP induces degeneration of nucleus pulposus cells in vitro. For in vivo experiments, lv-NC or lv-STING were injected into the central intervertebral disc space. The degeneration level of IVDD was assessed by MRI, X-ray, HE, and Safranin O staining. RESULTS: We found that the expression of STING was upregulated in human and rat degenerated NP tissue as well as in TBHP-treated NP cells. Overexpression of STING promoted the degradation of extracellular matrix; it also promoted apoptosis and senescence of TBHP-treated and untreated NP cells. Knock-down of STING significantly reversed these effects. Mechanistically, STING activated IRF3, whereas blockage of IRF3 attenuated STING-induced apoptosis, senescence and ECM degradation. In vivo experiments revealed that STING knock-down alleviated puncture-induced IVDD development. CONCLUSION: STING promotes IVDD progress via IRF3, while suppression of STING may be a promising treatment for IVDD.
Assuntos
Degeneração do Disco Intervertebral/metabolismo , Proteínas de Membrana/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose , Senescência Celular , Matriz Extracelular/patologia , Humanos , Fator Regulador 3 de Interferon/metabolismo , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/patologia , Imageamento por Ressonância Magnética , Núcleo Pulposo/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Regulação para Cima , Raios XRESUMO
BACKGROUND AND PURPOSE: Tirofiban administration during mechanical thrombectomy (MT) remains controversial. The aim was to evaluate the safety and efficacy of a low-dose rescue tirofiban regimen during MT for Chinese acute ischaemic stroke (AIS) patients. METHODS: Patients from the ANGEL study, a multicentric, prospective registry study that included AIS patients who underwent MT owing to proximal large-artery occlusion from June 2015 to December 2017, were collected. The patients were dichotomized into tirofiban and non-tirofiban groups according to whether rescue tirofiban was performed during MT. Safety outcomes [symptomatic intracerebral haemorrhage (sICH), total intracerebral haemorrhage (ICH) and distal embolization] and efficacy outcomes (artery recanalization and functional outcomes at 3-month follow-up) were compared between groups using logistic regression analysis. RESULTS: A total of 662 patients were included in this study, and 230 (34.7%) were in the tirofiban group. No significant differences in safety outcomes on sICH, total ICH and distal embolization and efficacy outcomes on artery recanalization and 3-month functional independence were observed between the tirofiban and non-tirofiban group in the entire cohort or the anterior circulation stroke or posterior circulation stroke patients (P > 0.05 for all groups). However, low-dose rescue tirofiban was significantly correlated with 3-month mortality reduction for posterior circulation stroke patients [adjusted hazard ratio 0.35 (0.14-0.92), P = 0.03]. CONCLUSIONS: Low-dose rescue tirofiban during MT was not associated with increased risk of sICH, ICH and distal embolization for AIS patients, and may be correlated with 3-month mortality reduction for posterior circulation stroke.
Assuntos
Tirofibana/uso terapêutico , Artérias , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Trombectomia , Resultado do TratamentoRESUMO
Objective: To explore the potential mechanism of sorafenib resistance associated long non-coding RNA (lncRNA-SRLR) promoted invasion and metastasis in U2OS osteosarcoma cells. Methods: We transfected U2OS cells with negative control lentivirus (LV-NC) or lncRNA-SRLR overexpressed lentivirus (LV-over/SRLR) particles. LV-NC and LV-over/SRLR stable transfected cells (U20S/NC and U20S/SRLR) were selected by primary cell culture medium containing puromycin. The mRNA expressions of lncRNA-SRLR and procollagen-lysine, procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The effect of lncRNA-SRLR on the invasion of U2OS cells were determined by wound-healing assay and Transwell migration assay. The effect of SRLR on the interleukin-6 (IL-6) secretion of U2OS cells was evaluated by enzyme-linked immunosorbent assay (ELISA) analysis. The subcellular distribution of SRLR in U2OS cells was detected by fluorescence in situ hybridization (FISH) analysis.The expression of PLOD2 in cells was detected by immunofluorescence (IF). The expressions of PLOD2 and focal adhesion kinase (FAK)/signal transducer and activator of transcription 3 (STAT3) signal pathway related proteins in U2OS/NC and U2OS/SRLR cells were detected by western blotting. Results: qRT-PCR assay showed that mRNA expressions of lncRNA-SRLR and PLOD2 in U2OS/SRLR cells were (3 964.97±0.05) and (2.77±0.11), respectively, significantly higher than those in U2OS/NC cells (P<0.001 or P<0.01). The results of wound-healing and Transwell migration assay showed that over-expression of SRLR markedly promoted the invasion ability of U2OS cells (P<0.05). The result of ELISA analysis showed that the IL-6 secretions in U2OS/NC or U2OS/SRLR cells were (125.38±11.22) pg/ml or (119.97±13.43) pg/ml, without statistical significance (P>0.05). The subcellular distribution assay revealed that lncRNA-SRLR is predominately located in the nucleus. The result of IF showed that compared with U2OS/NC cells, the expression of PLOD2 was up-regulated in U2OS/SRLR cells. The result of western blotting showed that over-expression of SRLR significantly increased the expression levels of PLOD2, phosphorylation (p)-FAK and p-STAT3 in U2OS cells (P<0.01). Conclusion: lncRNA-SRLR promotes invasion and metastasis of osteosarcoma by activating PLOD2-FAK/STAT3 signal axis.
Assuntos
Neoplasias Ósseas , Osteossarcoma , RNA Longo não Codificante , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Osteossarcoma/genética , Osteossarcoma/metabolismo , RNA Longo não Codificante/metabolismo , Sorafenibe/farmacologiaRESUMO
Objective: To investigate the relationship between human papillomavirus (HPV) integration and prognosis of cervical cancer patients. Methods: The data of 82 patients with cervical cancer treated in the Radiotherapy Department of Peking Union Medical College Hospital from October 2004 to June 2012 were retrospectively analyzed.The patients were divided into poor prognosis group (recurrence or metastasis after surgery and adjuvant radiotherapy) and good prognosis group based on a propensity score matching strategy.The HPV integration of the two groups were detected by whole exome sequencing to determine whether the integration sites were located in the common fragile sites (CFSs). HPV integration and integration into CFSs were compared between the two groups. Results: Among the enrolled 82 patients, 37 were divided in poor survival group and 45 in good survival group. A total of 90 integration breakpoints were identified, 30 of them occurred in poor prognosis group and 60 occurred in good prognosis group. In the poor prognosis group, HPV integration occurred in 20 patients, 13 of them were inserted in CFSs of 11 patients, and the numbers in good prognosis group were 26, 17, 11, respectively. There were no significantly statistical differences in the number of HPV integration events (P=0.289), HPV integration patients (P=0.735), CFSs integration events (P=0.427), and CFSs integration patients (P=0.591) between the two groups. In poor prognosis group, more CFSs integration events occurred in patients with metastasis than those in patients with only local recurrence (9 vs 2, P=0.003). Conclusions: No significant differences are observed in HPV integration and HPV integration into CFSs between cervical cancer patients with different prognoses. HPV integration into CFSs may be associated with distant metastasis.
Assuntos
Alphapapillomavirus , Neoplasias do Colo do Útero , Integração Viral , Alphapapillomavirus/genética , Feminino , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/virologia , Integração Viral/genéticaRESUMO
Objective: To investigate the effects of osimertinib on proliferation, migration and invasion of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) overexpressing HCC827 cells and explore the potential mechanism of PLOD2 induced osimertinib resistance. Methods: We transfected HCC827 cells with LV-vector and LV-over/PLOD2. The expression of PLOD2 was detected by quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. The effects of osimertinib on the proliferation of HCC827-vector and HCC827-PLOD2 cells were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. The effects of osimertinib on the migration and invasion of HCC827-vector and HCC827-PLOD2 cells were determined by Transwell assays. The expressions of E-cadherin and vimentin in cells were detected by immunofluorescence (IF). The expressions of epithelial-mesenchymal transition (EMT), FAK-PI3K/AKT and MAPK signal pathway related proteins were detected by western blotting. Results: The MTT assay showed that HCC827-PLOD2 cells were hyposensitive to osimertinib. The 50% inhibitory concentration (IC(50)) and resistance index of osimertinib for HCC827-PLOD2 cells was over 1 000 nmol/L and over 100, respectively. The result of wound healing assay showed that the migration distance of HCC827-PLOD2 was about (2.13±0.21) fold changes as that of HCC827-vector cells. The result of Transwell assay showed that the numbers of HCC827-PLOD2 passing through the matrix membrane were (212.78±10.43), significantly higher than (101.32±12.52) of HCC827-vector cells (P<0.01). The result of IF showed that compared with HCC827-vector cells, the expression of E-cadherin was down-regulated while vimentin was up-regulated in HCC827-PLOD2 cells. Osimertinb downregulated E-cadherin and upregulated vimentin expression in HCC827-vector cells but had limited effect in HCC827-PLOD2 cells. The result of western blotting showed that PLOD2 significantly increased vimentin expression level while decreased E-cadherin expression level. Osimertinib inhibited the expression of p-EGFR, but did not affect the expressions of PLOD2, p-FAK, p-AKT, p-ERK, vimentin and E-cadherin in HCC827-PLOD2 cells. Conclusion: PLOD2 confers resistance to osimertinib in HCC827 cells by regulating EMT, FAK-PI3K/AKT and MAPK signal pathways.
Assuntos
Acrilamidas/farmacologia , Compostos de Anilina/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/tratamento farmacológico , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Transição Epitelial-Mesenquimal , Humanos , Fosfatidilinositol 3-Quinases , Inibidores de Proteínas QuinasesRESUMO
Objective: To investigate the epidemiological characteristics for family clusters of COVID-19 in Zhejiang Province. Methods: The data including cases information of asymptomatic infected cases of family clusters of COVID-19 in Zhejiang Province were collected from Public Health Emergencies Reporting System of China Center for Disease Control and Prevention. Calculate the case number of subsequent cases, index cases, asymptomatic infected cases, exposure cases, and then, compute family secondary attack rate (SIR) and serial interval. Results: A total of 389 cases comprised 149 family index cases and 240 subsequent cases. The clinical symptoms between family index cases and subsequent cases (exclude asymptomatic infected cases ) were similar, fever was the most common symptoms in the two groups 115 (77.18%) and 110ï¼48.67%ï¼respectively, the cases with diarrhea symptoms accounted for the least proportion, which were 7 (4.70%) and 6 (2.65%) respectively. The serial interval between the family index cases and the subsequent cases [M (P25, P75)] was 4.00 (2.00, 6.00) days. Family secondary attack rate for subsequent cases was 34.43%, subsequent cases aged between 14 and 60 have the highest SIR (43.42%) compared with other two age groups, the difference was statistically (P<0.001); the family SIR of the spouses of the family index cases is 68.57%, and are higher than that of parents (29.03%), children (25.00%) and other family members (24.21%), the difference was also statistically (P<0.001). Conclusion: 2019 novel coronavirus has shorter serial interval and higher family SIR, the SIR of spouses is higher than other family members.
Assuntos
Infecções por Coronavirus/epidemiologia , Família , Pneumonia Viral/epidemiologia , Adolescente , Adulto , COVID-19 , China/epidemiologia , Análise por Conglomerados , Humanos , Pessoa de Meia-Idade , Pandemias , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: The efficacy of dual antiplatelet treatment may be modified by many factors. The aim was to assess whether the effect of clopidogrel plus aspirin versus aspirin alone on recurrent stroke would be affected by admission activated partial thromboplastin time (aPTT). METHODS: Data were derived from the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. A total of 5074 patients were categorized into three groups based on the aPTT distribution according to the 15th and 85th percentile. The primary outcome was any stroke within 90 days. The interaction of aPTT with antiplatelet therapy on stroke risk was assessed with a Cox proportional hazards model with adjustment for covariates. RESULTS: In the high aPTT group (defined as ≥35.9 s), stroke occurred in 6.7% of patients in the clopidogrel-aspirin arm and 11.9% in the aspirin arm [adjusted hazard ratio (HR) 0.50; 95% confidence interval (CI) 0.29-0.85]. In the medium aPTT group (24.6-35.8 s), stroke occurred in 7.7% of patients in the clopidogrel-aspirin arm and 11.8% in the aspirin arm (adjusted HR 0.62; 95% CI 0.50-0.75). Furthermore, in the low aPTT group (≤24.5 s), stroke occurred in 11.2% of patients in the clopidogrel-aspirin arm and 9.9% in the aspirin arm (adjusted HR 1.07; 95% CI 0.65-1.62). The interaction P value of antiplatelet therapy with aPTT level at the cut-point of approximately 25 s or below was significant (P < 0.05). CONCLUSIONS: Dual antiplatelet therapy was superior to single antiplatelet therapy in the high or medium aPTT group but not in the low aPTT group.
Assuntos
Aspirina/farmacologia , Isquemia Encefálica/prevenção & controle , Clopidogrel/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Tempo de Tromboplastina Parcial , Inibidores da Agregação Plaquetária/farmacologia , Acidente Vascular Cerebral/prevenção & controle , Idoso , Aspirina/administração & dosagem , Clopidogrel/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , RecidivaRESUMO
Mitigation of climate change depends on accurate estimation and mapping of terrestrial carbon stocks, particularly in carbon dense tropical forests. Allometric equations can be used to robustly estimate biomass of tropical trees, but often require tree height, which is frequently unknown. Researchers and practitioners must, therefore, decide whether to directly measure a subset of tree heights to develop diameterâ:âheight (D:H) equations or rely on previously published generic equations. To date, studies comparing the two approaches have been spatially restricted and/or not randomly allocated across the landscape of interest, making the implications of deciding whether or not to measure tree heights difficult to determine. To address this issue, we use inventory data from a systematic-random forest inventory across Gabon (102 forest sites; 42,627 trees, including 7,036 height-measured trees). Using plot-specific models of D:H as a benchmark, we compare the performance of a suite of locally fitted and commonly used generic models (parameterized national, georegional, and pantropical equations) across a variety of scales, and assess which abiotic, anthropogenic, and topographical covariates contribute the most to bias in height estimation. We reveal marked spatial structure in the magnitude and direction of bias in tree height estimation using all generic models, due at least in part to soil type, which compounded to substantial error in site-level AGB estimates (of up to 38% or 150 Mg/ha). However, two generic pantropical models (Chave 2014; Feldpausch 2012) converged to within 2.5% of mean AGB at the landscape scale. Our results suggest that some (not all) pantropical equations can extrapolate AGB across large spatial scales with minimal bias in estimated mean AGB. However, extreme caution must be taken when interpreting the AGB estimates from generic models at the site-level as they fail to capture substantial spatial variation in D:H relationships, which could lead to dramatic under- or over-estimation of site-level carbon stocks. Validated allometric models derived at site- or soil-type-levels may be the best way to reduce such biases arising from landscape-level heterogeneity in D:H model fit in the Afrotropics.
Assuntos
Carbono , Clima Tropical , Viés , Biomassa , Solo , ÁrvoresRESUMO
Objective: To test the effect of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) and/or osimertinib on the proliferation and apoptosis of HCC827 cells, and explore the potential mechanism of MALAT1 induced resistance to osimertinib. Methods: We transfected HCC827 cells with LV-vector or LV-over/MALAT1. Stable transfected cells (HCC827/Vector, HCC827/MALAT1) were selected by adding puromycin. HCC827/MALAT1 cells were further transfected with the shRNA-negative control (NC) or shRNA-human epidermal growth factor receptor 3 (ERBB3) plasmid. The effects of overexpression of MALAT1, knockdown of ERBB3 and/or osimertinib on the proliferation of HCC827 cells were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. Cell apoptosis induced by MALAT1 overexpression, knockdown of ERBB3 and/or osimertinib treatment were analyzed by flow cytometry analysis. The expressions of EGFR and ERBB3 signal pathway related proteins in HCC827 cells treated with overexpression of MALAT1, knockdown of ERBB3 and/or osimertinib treatment were detected by western blot. Results: The MTT assay showed that sensitivity to osimertinib of HCC827/MALAT1 cells were significantly repressed. The 50% inhibitive concentration (IC(50)) of osimertinib >4 000 nmol/L in HCC827/MALAT1 cells. However, knockdown of ERBB3 facilitated the anti-proliferation effect of osimertinib, and the IC(50) of osimertinib in shRNA-ERBB3 cells was (17.27±3.21) nmol/L. The results of flow cytometry analysis showed that the apoptotic rate of HCC827/MALAT1 cells induced by 10 nmol/L osimertinib was (8.38±0.92)%, significantly lower than (27.17±5.83)% of knockdown of ERBB3 (P<0.01). Western blotting showed that the expression of p-ERBB3, p-AKT and p-extracellular regulated protein kinases (ERK) in HCC827/MALAT1 cells was markedly up-regulated, while the expression of p-epithelial growth factor receptor (EGFR) was inhibited. The expressions of p-ERBB3, p-AKT and p-ERK were marginally affected by osimertinb. However, osimertinib downregulated the expressions of p-EGFR, p-ERBB3, p-AKT and p-ERK in ERBB3 deleted cells. Conclusions: MALAT1 confers resistance to osimertinb in HCC827 cells by activating of the ERBB3/PI3K/AKT and ERBB3/MAPK/ERK signaling pathways.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Piperazinas/uso terapêutico , RNA Longo não Codificante/metabolismo , Receptor ErbB-3/metabolismo , Acrilamidas , Compostos de Anilina , Biomarcadores Tumorais , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Receptor ErbB-3/genéticaRESUMO
Objective: To investigate the relationship of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) expression and the clinical characteristics of osteosarcoma, and explore the potential mechanism of tumour metastasis promoted by PLOD2. Methods: The expression of PLOD2 in osteosarcoma tissues and paired adjacent tissues were detected by immunohistochemistry and qRT-PCR. Correlation of PLOD2 expression in osteosarcoma with the clinical pathologic features was analyzed by Chi square test and Kaplan-Meier analysis.Fibrillar collagen formation and collagen deposition in the tumor tissues were detected by picrosirius red staining. We transfected U-2OS cells with LV-vector, LV-over/PLOD2, sh-NC and sh-PLOD2. The expression of PLOD2 was detected by qRT-PCR. The impact of POLD2 on U-2OS cell invasion was determined by wound-healing assay and Transwell migration assay. The expressions of PLOD2/FAK/JAK2-STAT3 signal pathway related proteins were detected by western blotting. Results: The high expression level of PLOD2 in osteosarcoma tissues was 72.5%, significantly higher than 0% in paired adjacent noncancerous tissues (P<0.01), the expression of PLOD2 was positively correlated with lymph node metastasis, pulmonary metastasis and poor outcome (P<0.01). The same results were also observed in qRT-PCR assay. The median survival time of patients with high expression of PLOD2 protein was 13 months, significantly shorter than 32 months of patients with low expression of PLOD2 (P<0.05). The result of picrosirius red staining showed that the percentage of collagen fiber deposition in the osteosarcoma tissue with high level of PLOD2 was (74.43+ 9.63)%, significantly higher than (9.67±1.28)% in tissue with low expression of PLOD2 (P<0.001). The result of wound-healing and Transwell migration assay showed that over-expression of PLOD2 markedly promoted the invasion, however, knockdown of PLOD2 suppressed the invasion of U-2OS cells (both P<0.01). The result of western blotting showed that over-expression of PLOD2 significantly increased the expression levels of p-FAK, p-JAK2, p-STAT3, but knockdown PLOD2 decreased the levels of p-FAK, p-JAK2, p-STAT3 in U-2OS cells. Conclusions: Up-regulation of PLOD2 in osteosarcoma is correlated with lymphatic and distant metastasis. PLOD2 promotes invasion and metastasis of osteosarcoma might through FAK/JAK2-STAT3 signal pathway.
Assuntos
Neoplasias Ósseas/patologia , Osteossarcoma/patologia , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo , Regulação para Cima , Humanos , Invasividade Neoplásica , Metástase NeoplásicaRESUMO
Objective: To investigate the safety and efficacy of mechanical thrombectomy in patients with atrial fibrillation complicated with acute intracranial arterial occlusion. Methods: Fifty-eight patients with atrial fibrillation complicated with acute intracranial arterial occlusion in the intervention group of East (Endovascular Therapy for Acute ischemic Stroke Trial) were analyzed. According to the TOAST (Trial of Org 10 172 in Acute Stroke Treatment) classification, patients were divided into ICAS (Intracranial Atherosclerotic Stenosis) group and cardiogenic embolism group. Clinical characteristics, treatment methods and clinical prognosis were compared between ICAS group and cardiogenic embolism group. Results: A total of 58 patients with atrial fibrillation complicated with acute intracranial arterial occlusion were included in this study, including 46 patients in the cardiogenic embolism group (79%) and 12 patients in the ICAS group (21%). The pre-hospital transport time in ICAS group was longer than that in cardiogenic embolism group (P<0.05).Patency rate in patients with atrial fibrillation complicated with acute intracranial arterial occlusion was 98.3% (57/58), The rate of patients with the 90-day function independent (mRS 0-2) was 51.7% (30/58). There were no statistically significant differences in functional independence, mortality rate, ICH and sICH at 90 days between the cardiogenic embolism group and the ICAS group. Conclusions: Mechanical thrombectomy is an effective method to treat patients with atrial fibrillation complicated with acute intracranial arterial occlusion.
Assuntos
Fibrilação Atrial , Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Artérias , Humanos , Estudos Retrospectivos , Trombectomia , Resultado do TratamentoRESUMO
Objective: To investigate the effect of microRNA-221 (miR-221) overexpression on gefitinib resistance in PC-9 cells and study its underlying mechanisms. Methods: PC-9 cells were transfected with LV-NC and LV-miR-221 to establish cell stabilizing strains (PC-9/NC and PC-9/miR-221), then they were used to detect the relative expression of miR-221 and apoptotic protease activating factor-1 (APAF-1) mRNA by real-time fluorescence quantitative PCR (qRT-PCR). The effects of gefitinib (0-4 µmol/L) on the growth and proliferation of cell stabilizing strains were detected by CCK-8 Assay. After gefitinib treatment, cell apoptosis was detected by Flow Cytometry Assays. The expression of epidermal growth factor receptor (EGFR), phosphorylated epidermal growth factor receptor (p-EGFR), APAF-1 and cleaved cysteinyl aspartate specific proteinase-3 (Cleaved-caspase-3) were detected by Western blot. Dual-Luciferase Reporter Assay was used to evaluate the relationship between APAF-1 and miR-221. Results: The relative expression of miR-221 in PC-9/NC cells was significantly lower than that in PC-9/miR-221 cells[(1.00±0.082) vs (40.24±0.017)](P<0.01). The half maximal inhibitory concentration (IC(50)) in PC-9/NC cells was significantly lower than that in PC-9/miR-221 cells[(IC(50)=0.1 µmol/L) vs (IC(50)>4 µmol/L)](P<0.05). Apoptosis rate of PC-9/NC cell was significantly higher than PC-9/miR-221[(33.42±4.28)% vs (10.27±1.12)%](P<0.05); APAF-1 mRNA expression was significantly higher in PC-9/NC cells than PC-9/miR-221[(1.000+ 0.069) vs (0.701±0.072)](P<0.05), and the expression of APAF-1 protein in PC-9/NC cells was significantly higher than that of PC-9/miR-221 cells. The dual luciferase reporter gene results showed that miR-221a inhibited luciferase activity significantly stronger than transfected miRNA negative control group after co-transfection of luciferase plasmids pmir-REPORT-APAF-1-wt and miR-221a mimics (P<0.01). p-EGFR was down-regulated in both PC-9/NC and PC-9/miR-221 cells after treatment with gefitinib. APAF-1 and Cleaved-caspase-3 proteins were significantly down-regulated in PC-9/miR-221 cells compared with PC-9/NC cells, while APAF-1 and Cleaved-caspase-3 proteins were up-regulated in PC-9/NC cells treated with gefitinib compared with PC-9/miR-221 cells (P<0.05). Conclusion: miR-221 induces resistance to gefitinib in PC-9 cells by downregulating APAF-1 expression.
Assuntos
MicroRNAs/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Gefitinibe , Regulação Neoplásica da Expressão Gênica , Humanos , RNA MensageiroRESUMO
Objective: To investigate the effect and mechanism of long non-coding RNA-metastasis associated lung adenocarcinoma transcript 1, (LncRNA-MALAT1) on invasion and metastasis of esophageal cancer cell EC-109. Methods: EC-109 cells were transfected with lentiviral vector carrying short hairpin RNA of MALAT1( shRNA-MALAT1) or a nonspecific shRNA control (shRNA-control). The expressions of MALAT1, microRNA-200a, ZEB1 and ZEB2 were detected by qRT-PCR. The effect of shRNA-MALAT1 on invasion of EC-109 cells was determined by transwell assay. The expressions of components of epithelial-msenchymal transition pathway in EC-109 cells were determined by immunofluorescence array and western blotting. The expression relationship between MALAT1 and miR-200a in EC-109 cells was detected by dual-luciferase reporter assay. Results: The result of qRT-PCR showed that the expressions levels of MALAT1, ZEB1 and ZEB2 in shRNA-MALAT1 group were 0.43±0.06, 0.64±0.04 and 0.51±0.04, respectively, significantly lower than 0.97±0.08, 1.06±0.07 and 0.98±0.05 in shRNA-control group and 1 in control group, respectively(all P<0.05). Transwell assay showed that the number of invaded cells in shRNA MALAT1 group was (96.81±10.43) per low-power field, markedly lower than that of (278.44±13.28) per low-power field in shRNA-control group (P<0.01). Immunofluorescence staining and Western blotting showed that MALAT1 downregulation significantly reduced the expressions of proteins related to EMT signal pathway in EC-109 cells.Dual luciferase reporter assay showed that compared to negative control, the activities of luciferase reporter in EC-109 cells co-transfected with pmirGLO-MALAT1-wt and miR-200a were significantly down-regulated. While co-transfected pmirGLO-MALAT1-mut with miR-200a mimics had no effect on the luciferase reporter activities of MALAT1. Conclusion: LncRNA MALAT1 functions as a competing endogenous RNA to regulate the expressions of ZEB1 and ZEB2 by sponging miR-200a and promotes invasion and migration of esophageal cancer cells through inducing epithelial-mesenchymal transition.
Assuntos
Transição Epitelial-Mesenquimal/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , RNA Longo não Codificante/fisiologia , Linhagem Celular Tumoral , Regulação para Baixo , Neoplasias Esofágicas/metabolismo , Genes Reporter , Proteínas de Homeodomínio/metabolismo , Humanos , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/metabolismo , Proteínas Repressoras/metabolismo , Transdução de Sinais , Transfecção/métodos , Homeobox 2 de Ligação a E-box com Dedos de Zinco , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismoRESUMO
Objective: To evaluate the efficacy and safety of neoadjuvant dose-dense or standard schedule chemotherapy with anthracyclines and taxanes for Luminal B (HER2-)Breast Cancer. Methods: From January 2010 to December 2014, 168 Luminal B (HER2-) breast cancer patients with stageâ ¡A-â ¢C confirmed by pathology were randomly assigned to receive one of the following regimens: (group A) concurrent TEC× 4 every 3 weeks, ( group B ) sequential EC× 4-T × 4 every 3 weeks, (group C ) dose-dense TEC× 4 every 2 weeks with G-CSF, (group D) sequential EC× 4(dose-dense)-T × 4 with dose-dense every 2 weeks . Results: A total of 168 patients completed the neoadjuvant chemotherapy as planned. The pathologic complete response (pCR) was 16.8% in the 4 groups.The pCR were 30.9% and 26.1% in the group C and group D respectively, significantly higher than patients with group A and group B(9.5%and 7.1%) ( P<0.05). Median follow-up was 43 months (IQR 3-63). The 3-year disease free survival (DFS) rate was 64.7%, 55.5%, 87.8% and 92.1% and the 3-year overall survival(OS)rate was 79.4%, 77.7%, 95.1%, 97.3% in the 4 groups respectively. Patients in the dose-dense group had better 3-year DFS and 3-year OS than those with the regular group.The side-effects could be evaluated in 154 patients.The incidence of neutropenia was 29.2% and 21.9% in the group C and group D versus 65.7%and 51.3% in the regular group(P<0.05), the incidence of nervous toxicity was 54.2%, 18.9%, 60.0%, 26.8% in the 4 groups respectively. The incidence of nervous toxicity in the dose-dense group was lower than that in the regular regimen group(P<0.05). Conclusion: Neoadjuvant dose-dense chemotherapy with anthracyclines and taxanes for Luminal B (HER2-)Breast Cancer was effective and can improve the pCR, DFS and OS.Comparing the two dose dense regimens, sequentially with anthracyclines and taxanes, the incidence of nervous toxicity were lower.