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BACKGROUND: The focus of medicine is shifting from treatment to preventive care. The expression of biomarkers of dementia and Alzheimer's disease (AD) appear decades before the onset of observable symptoms, and evidence has emerged supporting pharmacological and non-pharmacological interventions to treat modifiable risk factors of dementia. However, there is limited research on the epidemiology, clinical phenotypes, and underlying pathobiology of cognitive diseases in Asian populations. OBJECTIVES: The objectives of the Biomarkers and Cognition Study, Singapore(BIOCIS) are to characterize the underlying pathobiology of Cognitive Impairment through a longitudinal study incorporating fluid biomarker profiles, neuroimaging, neuropsychological and clinical outcomes in a multi-ethnic Southeast Asian population. DESIGN, SETTING, PARTICIPANTS: BIOCIS is a 5-year longitudinal study where participants are assessed annually. 2500 participants aged 30 to 95 will be recruited from the community in Singapore. To investigate how pathology presents with or without minimal clinical symptoms and vice versa, CI and unimpaired individuals will be recruited. Participants will undergo assessments to characterise biomarkers of dementia through neuroimaging, fluid biomarkers, cognitive assessments, behavioural and lifestyle profiles, retinal scans and microbiome indicators. RESULTS: Since commencement of recruitment in February 2022, 1148 participants have been enrolled, comprising 1012 Chinese, 62 Indian, and 35 Malay individuals. Mean age and education is 61.32 years and 14.34 years respectively with 39.8% males. 47.9 % of the cohort are employed and 32.06% have a family history of dementia. The prevalence of cerebral small vessel disease is 90.2% with a mean modified Fazekas white matter hyperintensity score of 4.1. CONCLUSION: The BIOCIS cohort will help identify novel biomarkers, pathological trajectories, epidemiology of dementia, and reversible risk factors in a Southeast Asian population. Completion of BIOCIS longitudinal data could provide insights into risk-stratification of Asians populations, and potentially inform public healthcare and precision medicine for better patient outcomes in the prevention of Alzheimer's disease and dementia.
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Biomarcadores , Disfunção Cognitiva , Humanos , Singapura/epidemiologia , Estudos Longitudinais , Masculino , Idoso , Pessoa de Meia-Idade , Feminino , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Adulto , Idoso de 80 Anos ou mais , Testes Neuropsicológicos , Cognição/fisiologia , Neuroimagem , Demência/epidemiologia , Demência/diagnóstico , Projetos de PesquisaAssuntos
Consenso , Fatores Imunológicos , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , China , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêutico , Administração Tópica , PapillomaviridaeRESUMO
Objective: To explore the clinical risk factors and susceptibility genes of diabetes after kidney transplantation (PTDM) and construct a risk prediction model for PTDM. Methods: The data of kidney transplant recipients who underwent follow-up in the Affiliated Lihuili Hospital, Ningbo University and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2001 to December 2022 were retrospectively analyzed. The recipients were divided into PTDM group and Non-PTDM group according to whether they were complicated with PTDM. The differences in clinical indicators between the two groups were compared, the risk factors affecting the incidence of PTDM were determined, and susceptibility genes of PTDM were screened by genome-wide association study (GWAS). PTDM risk prediction models based only on clinical indicators (Model 1) and clinical indicators combined with susceptibility genes (Model 2) were established respectively, and the predictive performance of the two prediction models was compared. Finally, the Nomogram of the optimal model was drawn, and the discrimination, calibration and clinical applicability of the model were evaluated. Results: A total of 113 kidney transplant recipients (70 males and 43 females) were included, with an average age of (46.2±10.8) years. There were 51 cases in PTDM group and 62 cases in Non-PTDM group. The related factors screened by GWAS and logistic regression analysis included family history of diabetes (OR=88.912, 95%CI: 5.827-1 356.601, P=0.001), preoperative triglyceride (TG) (OR=1.888, 95 %CI: 1.150-3.098, P=0.012), uric acid (UA) (OR=1.011, 95%CI: 1.000-1.022, P=0.045) and rs802707 (OR=10.046, 95%CI: 1.462-69.042, P=0.019). The area under the curve (AUC) of the receiver operating characteristics analysis (ROC) predicted by Model 1 for PTDM was 0.891 (95%CI: 0.811-0.972), with the sensitivity of 0.889 and the specificity of 0.742. The AUC of ROC curve predicted by Model 2 for PTDM was 0.930 (95%CI: 0.864-0.995), with the sensitivity of 0.885 and the specificity of 0.900. Conclusions: Family history of diabetes, preoperative TG and UA, and rs802707 are significantly associated with the occurrence of PTDM. In addition, the combination of susceptibility genes could improve the predictive ability of clinical indicators for the risk of PTDM.
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Diabetes Mellitus , Transplante de Rim , Feminino , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Estudo de Associação Genômica Ampla , Estudos Retrospectivos , Fatores de Risco , Triglicerídeos , Ácido ÚricoRESUMO
Fe3O4/CNT composites are synthesized with ethylene glycol as solvent by a one-step solvothermal method and used as anode materials for asymmetric supercapacitors (ASC). An appropriate amount of water in ethylene glycol can accelerate the formation of Fe3O4and reduce the average size of Fe3O4to around 20 nm. However, spherical Fe3O4particles larger than 100 nm will form in pure ethylene glycol for long reaction time. The Fe3O4/CNT composite with small Fe3O4nanoparticles exhibits a high specific surface area, promoted electron transfer ability, as well as a high utilization rate of active materials. The optimized electrode shows a high specific capacity of 689 C g-1at 1 A g-1, and remains 443 C g-1at 10 A g-1. The inferior long-term cycling stability is due to the phase transition of Fe3O4and a reductive effect to form metallic Fe. An ASC using Fe3O4/CNT and NiCoO2/C composites as anode and cathode, respectively, delivers a high energy density of 58.1 Wh kg-1at a power density of 1007 W kg-1in a voltage window of 1.67 V and has a capacity retention of 63% after 5000 cycles. The self-discharge behavior of the ASC is also investigated.
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Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) â and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINâ ¡ and more lesions after treatment with CINâ ¡ or CIN â ¢ (CINâ ¡/CIN â ¢). All participants were randomly divided into the test group and the control group at a ratio of 2â¶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ2=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ2=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.
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Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Infecções por Papillomavirus/diagnóstico , Esqueleto da Parede Celular , Infecção Persistente , Pós , Displasia do Colo do Útero/patologia , Imunoterapia , PapillomaviridaeRESUMO
Presbyopia is a physiological aging situation that the plasticity and elasticity of the lens and the function of the ciliary muscle become weaker, resulting in a decreased accommodation and inability to focus on near objects. Nowadays, there are many clinical strategies to correct presbyopia, each of which has its own advantages and disadvantages, however, there is no true sense of way to restore accommodation function. This article reviews both worldwide and domestic research on presbyopia, and analyzes and summaries the status quo as well as research progress of presbyopia correction modalities, surgical approaches, and drug therapies, hoping to provide a reference for clinical works.
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Cristalino , Presbiopia , Humanos , Presbiopia/cirurgia , Acomodação Ocular , Corpo Ciliar , Envelhecimento/fisiologiaRESUMO
Objective: To evaluate the value of the 2020 diagnostic criteria (Cellucci criteria) for pediatric autoimmune encephalitis (AE) in children with suspected AE in a single center. Methods: The clinical data of 121 children hospitalized at the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2021, with a diagnosis of suspected AE, were retrospectively collected and analyzed. The children were divided into definite antibody-positive AE (dAPAE), probable antibody-negative AE (prANAE), possible AE (pAE) and non-AE groups according to the Chinese expert consensus and the Graus criteria. A new diagnosis was made according to the Cellucci criteria which was compared with the clinical diagnosis to evaluate the diagnostic value of the Cellucci criteria. The Mann-Whitney U test, Kruskal-Wallis test, and χ2 test were used to compare the differences among groups. The sensitivity and specificity were used to evaluate efficacy of the Cellucci criteria. Results: Among the 121 children, 72 were males and 49 were females, with an age of 10.3 (6.5, 14.0) years at disease onset. There were 99 cases diagnosed as AE according the clinical diagnosis (58 males and 41 females), of which 43 cases were diagnosed as dAPAE, 14 cases as prANAE and 42 cases as pAE, and the other 22 cases were not AE (14 males and 8 females). The top 2 initial symptoms in the 99 children with AE were seizures (53 cases, 53.5%) and abnormal mental behaviors (35 cases, 35.4%). And the most common symptoms during the course of the disease were abnormal mental behaviors (77 cases, 77.8%) and seizures (64 cases, 64.6%). There were statistically differences in the incidence of consciousness disorders, autonomic dysfunctions during the course of the disease and the length of hospitalization among the 4 groups (χ2=21.63, 13.74, H=22.60, all P<0.05). Ninety-six of the 121 children were tested for AE-related antibodies, of which 45 cases (46.9%) were antibody-positive. According to the Cellucci criteria, 42 cases were diagnosed as dAPAE, 34 cases as prANAE and 14 cases as pAE. Compared with the clinical diagnosis, the sensitivity of the Cellucci criteria for the diagnosis of the 3 types of AE were 93.02%, 92.86% and 87.88%, and the specificity were 96.23%, 74.39% and 86.36%, respectively. Conclusions: The Cellucci criteria has a high sensitivity and specificity for the diagnosis of pAE and dAPAE in the clinical management of children with suspected AE, while a high sensitivity but low specificity for the diagnosis of prANAE. Therefore, it is recommended to apply the Cellucci criteria selectively in clinical practice according to the actual situation, especially in the diagnosis of prANAE.
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Encefalite , Doença de Hashimoto , Criança , Encefalite/diagnóstico , Feminino , Doença de Hashimoto/diagnóstico , Humanos , Masculino , Estudos Retrospectivos , ConvulsõesAssuntos
Arthrodermataceae , Tinha , Humanos , Masculino , Microsporum , Escroto , Tinha/complicações , Tinha/diagnósticoAssuntos
Carcinoma , Neoplasias Parotídeas , Humanos , Masculino , Proteínas Nucleares , Glândula Parótida , TestículoRESUMO
Because hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels modulate the excitability of cortical and hippocampal principal neurons, these channels play a key role in the hyperexcitability that occurs during the development of epilepsy after a brain insult, or epileptogenesis. In epileptic rats generated by pilocarpine-induced status epilepticus, HCN channel activity is downregulated by two main mechanisms: a hyperpolarizing shift in gating and a decrease in amplitude of the current mediated by HCN channels, Ih. Because these mechanisms are modulated by various phosphorylation signaling pathways, we hypothesized that phosphorylation changes occur at individual HCN channel amino acid residues (phosphosites) during epileptogenesis. We collected CA1 hippocampal tissue from male Sprague Dawley rats made epileptic by pilocarpine-induced status epilepticus, and age-matched naïve controls. We also included resected human brain tissue containing epileptogenic zones (EZs) where seizures arise for comparison to our chronically epileptic rats. After enrichment for HCN1 and HCN2 isoforms by immunoprecipitation and trypsin in-gel digestion, the samples were analyzed by mass spectrometry. We identified numerous phosphosites from HCN1 and HCN2 channels, representing a novel survey of phosphorylation sites within HCN channels. We found high levels of HCN channel phosphosite homology between humans and rats. We also identified a novel HCN1 channel phosphosite S791, which underwent significantly increased phosphorylation during the chronic epilepsy stage. Heterologous expression of a phosphomimetic mutant, S791D, replicated a hyperpolarizing shift in Ih gating seen in neurons from chronically epileptic rats. These results show that HCN1 channel phosphorylation is altered in epilepsy and may be of pathogenic importance.
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Epilepsia do Lobo Temporal , Epilepsia , Animais , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Masculino , Espectrometria de Massas , Fosforilação , Canais de Potássio/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Globally, cervical cancer continues to be one of the most common cancers among females. Although screening for cervical cancer has been gradually carried out, the incidence and mortality of cervical cancer in China are still at a high level. So the prevention and treatment of cervical cancer in China still has lots of work to do. The International Federation of Obstetrics and Gynecology (FIGO) gynecological oncology committee revised the staging of cervical cancer in 2018. The new staging changed in terms of stage â B and stage â ¢ compared with previous FIGO staging. FIGO also provided prevention and treatment strategies and the treatment regimens of each stage, which had an important impact on the prevention and treatment of cervical cancer as well as an important enlightenment for China.
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Estadiamento de Neoplasias/métodos , Neoplasias do Colo do Útero/patologia , China , Feminino , Humanos , Neoplasias do Colo do Útero/terapiaRESUMO
OBJECTIVE: This study explored the effect of miR-26a-5p on cell proliferation, migration, and invasion in gastric cancer by targeting COL10A1. MATERIALS AND METHODS: First, differentially expressed genes were identified from microarray GSE103236 data of human gastric cancer. Then, qRT-PCR was carried out to detect the expression levels of COL10A1 and miR-26a-5p in gastric cancer cells and normal cases. The CCK-8 method was used to test cell proliferation. The colony formation assay was performed for the examination of the cell colony-forming ability, and transwell was applied for the detection of cell migration and invasion. Subsequently, the targeted relationship between miR-26a-5p and COL10A1 was identified by bioinformatics methods and further verified by Dual-Luciferase assay. The rescue experiment was finally conducted to validate the miR-26a-5p-dependent mechanism on cell proliferation, migration, and invasion via targeting COL10A1. RESULTS: COL10A1 was found to be highly expressed in gastric cancer cells, while miR-26a-5p was poorly expressed. Silencing COL10A1 inhibited cell proliferation, migration, and invasion in gastric cancer. Besides, miR-26a-5p could function on gastric cancer cells by reducing COL10A1. As well, the rescue experiment suggested that the down-regulation of COL10A1 could reverse the inhibitory effect of miR-26a-5p on gastric cancer cells. CONCLUSIONS: Collectively, miR-26a-5p can potentiate proliferation, migration, and invasion of gastric cancer cells by targeting COL10A1.
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Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Colágeno Tipo X/biossíntese , MicroRNAs/biossíntese , Neoplasias Gástricas/metabolismo , Linhagem Celular Tumoral , Colágeno Tipo X/antagonistas & inibidores , Colágeno Tipo X/genética , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
Objective:To explore the signal pathway that mediates the effect of 2-methoxyestradiolï¼2ME2ï¼ on human laryngeal papilloma cell line, in terms of cell proliferation and neovascularization. Method:HIF-1α expression of human laryngeal papilloma cell lineï¼Hs840. Tï¼ was interfered using siRNA, and the cells were then processed by 2ME2 in two concentrations. RT-PCR and ELISA were performed to detect the difference of HIF-1α in cells with normal or lower HIF-1α mRNA level, with ELISA test of excretory VEGF level and CCK8 test of cell viability. Result:The ICî50of 2ME2 in Hs840. T was 0.309 µmol/L in terms of the inhibition effect of cell proliferationï¼P<0.01ï¼. Baseline level of intracellular HIF-1α was detectable, and procession of Hs840. T cells by 2ME2 of 0.4 µmol/L inhibited the transcription and expression of HIF-1α byï¼76.8±2.0ï¼% andï¼68.6±3.5ï¼% [vs blank groupï¼100.0±2.7ï¼% andï¼100.0±6.9ï¼%, P<0.01]. VEGF excretion decreased toï¼50.8±2.1ï¼ andï¼28.1±4.0ï¼% [vs blank groupï¼100.0±3.1ï¼%, P<0.01]after procession by 2ME2 of 0.2 µmol/L and 0.4 µmol/L. After the successful interference of HIF-1α by siRNA, the inhibition effect on cell proliferation by 2ME2 of 0.4 µmol/L decreased toï¼51.5±3.8ï¼% [vs control groupï¼65.7±1.7ï¼%, P<0.01]. siRNA interference of HIF-1α lead to a decrease of HIF-α mRNA and protein level toï¼16.3±0.9ï¼% andï¼7.4±0.8ï¼% [vs cells not interferedï¼76.8±2.0ï¼% vsï¼68.6±3.5ï¼%, P<0.01]. Secretory VEGF dropped toï¼41.0±2.9ï¼% [vs cells not interferedï¼28.1±4.0ï¼%, P<0.05]. Conclusion:2ME2 has a significant inhibitory effect on human laryngeal cell line. The inhibition of cell proliferation was mediated by a lower level of HIF-1α and therefore lower VEGF. 2ME2 might serve as a novel potential therapy for patients of recurrent respiratory papillomatosis.
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2-Metoxiestradiol/metabolismo , Linhagem Celular Tumoral , Estradiol , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Laríngeas , Papiloma , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Objective: To analyze the clinical characteristics, treatment and prognosis of chyle leakage after central lymph node dissection for thyroid cancer. Methods: A retrospective analysis was made of 985 patients who underwent surgical for thyroid carcinoma plus central lymph node dissection from January 2017 to June 2018 in Renji Hospital Affiliated to Medical College of Shanghai Jiaotong University. Patients were divided into those without (group A, n=973) and with (group B, n=12) chyle leakage. Patients with chyle leakage who underwent left central lymph node dissection were divided into group B1 (n=5) and right central lymph node dissection into group B2 (n=7). Patients with chyle leakage were treated with fat-free diet and negative pressure drainage. SPSS 20.0 software was used to analyze the general condition, surgical pathology, postoperative drainage, hospitalization days, treatment and prognosis of patients in B1 and B2 groups. Results: The incidence of chyle leakage after central lymph node dissection for thyroid cancer was 1.2% (12/985). There were no significant differences in age, sex, size of primary lesion, number of lymph node dissection in central area and number of lymph node metastasis in central area between group A and group B (all P>0.05). The drainage volume on the first day after operation [((51.7±26.7)) ml] and the average hospitalization days [(3.4±0.8) d] in group A were significantly lower than those in group B ([131.3±56.0)]ml, [10.4±2.6)]d). The differences were statistically significant (t value was -5.442, -11.238, respectively, both P<0.001). There were no significant differences in age, size of primary lesion, number of lymph node dissection, number of lymph node metastasis, drainage volume on the first day after operation and average hospitalization days between group B1 and group B2 (all P>0.05). All chyle leakages in group B stopped after conservative management without surgical intervention. Conclusion: The occurrence of chyle leakage after central lymph node dissection is a rare complication. It can be cured by conservative treatment such as diet control, pressure bandaging and negative pressure drainage, and generally does not require secondary surgery.
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Quilo , Doenças Linfáticas/terapia , Sistema Linfático/lesões , Esvaziamento Cervical/efeitos adversos , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , China , Humanos , Doenças Linfáticas/etiologia , Sistema Linfático/patologia , Sistema Linfático/cirurgia , Esvaziamento Cervical/métodos , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodosRESUMO
A single-ridged K-band circularly polarized horn antenna offering excellent performance has been developed by improving the polarization conversion and manufacturing complexity. The numerical and experimental results are consistent showing the return loss of this antenna to be less than -20 dB and the axial ratio at the boresight direction to be less than 0.7 dB in the frequency range from 23.5 GHz to 24.5 GHz. In addition, the gain of this antenna is higher than 20 dB. The newly designed circularly polarized horn antenna has a simple structure and outperforms many existing circular polarization devices in high-power operations.
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Hilar cholangiocarcinoma is one of the most difficult malignant tumors to treat in the biliary system. In Japan, 5-year survival rate of the disease has increased from 32.5% to 67.1% during the past 30 years. The impressive progress reflects the solid efforts in preoperative endoscopic diagnosis, innovation in surgery such as PTPE as well as hepato-pancreatoduodenectomy and perioperative treatment including replacement of the bile and synbiotic treatment, which have finally formed a set of standardized diagnosis and treatment systems. The present review intends to report the history, current status and remaining bottlenecks of the diagnosis and treatment system of hilar cholangiocarcinoma in Japan as follows.
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Neoplasias dos Ductos Biliares , Tumor de Klatskin , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Intra-Hepáticos , Hepatectomia , Humanos , Japão , Tumor de Klatskin/diagnóstico , Tumor de Klatskin/terapia , Resultado do TratamentoRESUMO
Essentials Recombinant von Willebrand factor (rVWF) is effective in von Willebrand disease (VWD). A phase 3 study of rVWF, with/without recombinant factor VIII (rFVIII) before surgery in VWD. Overall rVWF's efficacy was rated excellent/good; rVWF was administered alone in most patients. rVWF was well-tolerated and hemostasis was achieved in patients with severe VWD undergoing surgery. SUMMARY: Background Recombinant von Willebrand factor (rVWF) has demonstrated efficacy for on-demand treatment of bleeding in severe von Willebrand disease (VWD), warranting evaluation in the surgical setting. Objectives This study (NCT02283268) evaluated the hemostatic efficacy/safety profile of rVWF, with/without recombinant factor VIII (rFVIII), in patients with severe VWD undergoing surgery. Patients/Methods Patients received rVWF 40-60 IU kg-1 , VWF ristocetin cofactor activity was measured 12-24 h before surgery. If endogenous FVIII activity (FVIII:C) target levels were achieved 3 h before surgery, rVWF was administered alone 1 h before surgery; rVWF was co-administered with rFVIII if target endogenous FVIII levels were not achieved. rVWF was infused postoperatively to maintain target trough levels. Overall and intraoperative hemostatic efficacy, the pharmacodynamics of rVWF administration and the incidence of adverse events (AEs) were assessed. Results All patients treated with rVWF for major (n = 10), minor (n = 4) and oral (n = 1) surgery had overall and intraoperative hemostatic efficacy ratings of excellent (73.3% and 86.7%) or good (26.7% and 13.3%). Most rVWF infusions (89.4%) were administered alone, resulting in hemostatically effective levels of endogenous FVIII within 6 h, which were sustained for 72-96 h; 70% (n = 7/10) of major surgeries were performed without rFVIII co-administration. Six patients reported 12 treatment-emergent AEs. Two patients each had one serious AE: diverticulitis (not treatment related) and deep vein thrombosis (sponsor-assessed as possibly treatment related). No severe allergic reactions or inhibitory antibodies were reported. Conclusions These data support the efficacy and safety profile of rVWF in patients with severe VWD undergoing elective surgery.
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Perda Sanguínea Cirúrgica/prevenção & controle , Coagulantes/administração & dosagem , Procedimentos Cirúrgicos Eletivos , Hemostasia/efeitos dos fármacos , Doenças de von Willebrand/tratamento farmacológico , Fator de von Willebrand/administração & dosagem , Adulto , Idoso , Coagulantes/efeitos adversos , Coagulantes/farmacocinética , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem , Doenças de von Willebrand/sangue , Doenças de von Willebrand/complicações , Doenças de von Willebrand/diagnóstico , Fator de von Willebrand/efeitos adversos , Fator de von Willebrand/farmacocinéticaRESUMO
Objective: To study the prevalence of high-risk HPV (HR HPV) in women who accepted cervical cancer screening in Beijing and its distribution in cervical precancerous lesions. Methods: From January 2014 to March 2015, all women aged 35-64 years old and received free screening in institutions of cervical cancer in Beijing were recruited. Stratified cluster random sampling method was used in selecting 31 091 women for gynecological examination and genotyping of HR-HPV. Those positive for HR-HPV (except for HPV 16/18) were examined for cervical cell. For those atypical squamous cells of uncertain significance (ASCUS) and above, who were positive for HPV 16/18 and with uncertain results for cervical cell, were transferred for colposcopy examination. For those with suspicious or abnormal results for colposcopy, were transferred for histopathology. The prevalence of HR-HPV, cervical cancer and precancerous lesions among the participants were analyzed. Results: Totally 31 091 women aged from 35-year-old to 64-year-old, with 44.3% (13 780 women) in the 35-49 age group and 55.7% (17 311 women) in the 50-64 age group. 66.1% (20 536 women) were rural women. The infection rate of HR-HPV was 7.4%(2 305 cases) among the women. High-risk infection rates of HPV except HPV 16/18 were 5.7% (1 758 cases), and multi-infection rate was 1.5% (477 cases). The highest infection rate was 7.9% (1 044 cases) among the 45-49 year-old and 50-54 year-old age groups (χ(2)=14.07, P=0.015). The rate in rural women was significantly higher than that of the urban women (6.2%, 507 cases; 7.9%, 1 798 cases) (χ(2)=25.75, P<0.001). The proportion of HPV16, HPV18, HPV52, HPV51, HPV58 was 17.0% (391 cases), 6.9% (161 cases), 8.6% (20 cases), 5.2% (12 cases) and 7.7% (18 cases), respectively. The detection rate of cervical cancer and precancerous lesions in the population was 395.6/100 000 (123 cases). In high-grade squamous intraepithelial lesions (HSIL), HPV16 and 18 infections accounted for 60.5% (72 cases) of all. HPV16 infection rate and detection rate of HSIL were the highest in 50-54 year-old group which were 1.5% (107 cases) and 25.2% (30 cases) (χ(2)=11.54, P=0.042). Conclusion: Top five types of HR-HPV infection in women who accepted cervical cancer screening in Beijing were HPV16, 18, 52, 51 and 58. The infection rate of HPV16 and 18 increased significantly in HSIL women. HPV16 infection rate and detection rate of HSIL were the highest in 50-54 year-old age group.
Assuntos
Papillomavirus Humano 16 , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/virologia , Adulto , Células Escamosas Atípicas do Colo do Útero , Pequim , Colposcopia , Detecção Precoce de Câncer , Feminino , Genótipo , Papillomavirus Humano 18 , Humanos , Pessoa de Meia-Idade , Papillomaviridae , Gravidez , Prevalência , Displasia do Colo do ÚteroRESUMO
Objective:The aim of this study is to analyze the different expression and function of androgen receptors (AR) and estrogen receptor (ER-α) in laryngeal squamous cell carcinoma (LSCC). In combination with the expression of prolactin receptor (PRLR), we analyzed the prognostic impact of three receptors on the laryngeal carcinoma. Method:In this study, immunohistochemistry and reverse transcription polymerase chain reaction (RT-PC) analysis were performed on the tumor tissues and adjacent normal tissues in 112 LSCC patients (95 males and 17 females). We found that hormone receptor expression is closely related to the clinical tumor lesions and overall survival data. Result:The expression of AR, ER-α and PRLR in tumor tissues were much higher than those in adjacent normal tissues (P>0.05) at both protein and mRNA levels. The higher PRLR level indicate poor survival in LSCC patients (P=0.02), while higher ER-α expression could influence the survival with considerable trend toward significance (P=0.06). Furthermore, the higher expression of ER-α in tumours were corresponding with PRLR cytoplasmic higher level expression (r=0.802, P=0.04). This mutual promoted effect between ER-α and PRLR possibly suggests potential mechanisms among those sex related hormone receptors in laryngeal cancer. Conclusion:It has become increasingly credible that the sex related hormone receptors play an important role in the development of LSCC.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Laríngeas/metabolismo , Receptores Androgênicos/metabolismo , Receptores de Estrogênio/metabolismo , Receptores da Prolactina/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Laríngeas/patologia , Masculino , PrognósticoRESUMO
OBJECTIVE: Osteosarcoma is the most frequent primary bone malignancy that affects young adults and adolescents around the world. Increasing evidence suggests that dysfunctions of microRNAs (miRNAs) used to play an important role in human cancers. We aimed at evaluating the potential function of miR-16 and verify its influence on the function of RAB23 in osteosarcoma. PATIENTS AND METHODS: miR-16 expressions in osteosarcoma tissues and cell lines were examined using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Transwell chambers were conducted to detect the miR-16 effects on osteosarcoma cells migration and invasion. Meanwhile, Western blot and luciferase assays were performed to validate RAB23 as miR-16 targets. RESULTS: miR-16 was down-regulated in osteosarcoma cell lines (MG63, SAOS-2, U2OS, and SOSP-9607) and osteosarcoma specimens, while RAB23 expression was higher in tumor tissues. Ectopic over-expression of miR-216 in osteosarcoma cells could inhibit cells migration and invasion. RAB23 was confirmed as a direct target of miR-16 and the inverse relationship between them was also observed. Over-expression of RAB23 ablates the inhibitory effects of miR-16. CONCLUSIONS: miR-16 inhibited cancer migration and invasion, and promoted the RAB23 expression in osteosarcoma. This newly identified miR-16/RAB23 axis may provide new insight into the pathogenesis and represents a potential therapeutic target for osteosarcoma.