RESUMO
Objective: To investigate the molecular mechanisms of chronic rhinosinusitis (CRS), to identify key cell subgroups and genes, to construct effective diagnostic models, and to screen for potential therapeutic drugs. Methods: Key cell subgroups in CRS were identified through single-cell transcriptomic sequencing data. Essential genes associated with CRS were selected and diagnostic models were constructed by hdWGCNA (high dimensional weighted gene co-expression network analysis) and various machine learning algorithms. Causal inference analysis was performed using Mendelian randomization and colocalization analysis. Potential therapeutic drugs were identified using molecular docking technology, and the results of bioinformatics analysis were validated by immunofluorescence staining. Graphpad Prism, R, Python, and Adobe Illustrator software were used for data and image processing. Results: An increased proportion of basal and suprabasal cells was observed in CRS, especially in eosinophilic CRS with nasal polyps (ECRSwNP), with P=0.001. hdWGCNA revealed that the "yellow module" was closely related to basal and suprabasal cells in CRS. Univariate logistic regression and LASSO algorithm selected 13 key genes (CTSC, LAMB3, CYP2S1, TRPV4, ARHGAP21, PTHLH, CDH26, MRPS6, TENM4, FAM110C, NCKAP5, SAMD3, and PTCHD4). Based on these 13 genes, an effective CRS diagnostic model was developed using various machine learning algorithms (AUC=0.958). Mendelian randomization analysis indicated a causal relationship between CTSC and CRS (inverse variance weighted: OR=1.06, P=0.006), and colocalization analysis confirmed shared genetic variants between CTSC and CRS (PPH4/PPH3>2). Molecular docking results showed that acetaminophen binded well with CTSC (binding energy:-5.638 kcal/mol). Immunofluorescence staining experiments indicated an increase in CTSC+cells in CRS. Conclusion: This study integrates various bioinformatics methods to identify key cell types and genes in CRS, constructs an effective diagnostic model, underscores the critical role of the CTSC gene in CRS pathogenesis, and provides new targets for the treatment of CRS.
Assuntos
Catepsina C , Rinossinusite , Transcriptoma , Humanos , Algoritmos , Doença Crônica , Biologia Computacional , Perfilação da Expressão Gênica , Aprendizado de Máquina , Análise da Randomização Mendeliana , Simulação de Acoplamento Molecular , Pólipos Nasais/genética , Rinossinusite/genética , Análise de Célula Única , Catepsina C/genéticaRESUMO
Recent demonstrations of room-temperature lasing in optically pumped GeSn show promise for future CMOS compatible lasers for Si-photonics applications. However, challenges remain for electrically pumped devices. Investigation of the processes that limit device performance is therefore vital in aiding the production of future commercial devices. In this work, a combined experimental and modelling approach is utilised to explore the dominant loss processes in current devices. By manipulating the band structure of functioning devices using high hydrostatic pressure techniques at low temperature, the dominant carrier recombination pathways are identified. This reveals that 93 ± 5% of the threshold current is attributable to defect-related recombination at a temperature, T = 85 K. Furthermore, carrier occupation of L-valley states (carrier leakage) is responsible for 1.1 ± 0.3% of the threshold current, but this sharply increases to 50% with a decrease of just 30 meV in the L- Γ separation energy. This indicates that thermal broadening of a similar order may reproduce these adverse effects, limiting device performance at higher temperatures. Temperature dependent calculations show that carrier occupation of indirect valley L-states strongly affects the transparency carrier density and is therefore very sensitive to the Sn composition, leading to an effective operational temperature range for given Sn compositions and strain values. Recommendations for future device designs are proposed based on band structure and growth optimisations.
RESUMO
Objective: To explore the value of cardiac magnetic resonance imaging (CMR) in the risk stratification of hypertrophic cardiomyopathy (HCM). Methods: HCM patients who underwent CMR examination in Fuwai Hospital between March 2012 and May 2013 were retrospectively enrolled. Baseline clinical and CMR data were collected and patient follow-up was performed using telephone contact and medical record. The primary composite endpoint was sudden cardiac death (SCD) or and equivalent event. The secondary composite endpoint was all-cause death and heart transplant. Patients were divided into SCD and non-SCD groups. Cox regression was used to explore risk factors of adverse events. Receiver operating characteristic (ROC) curve analysis was used to assess the performance and the optimal cut-off of late gadolinium enhancement percentage (LGE%) for the prediction of endpoints. Kaplan-Meier and log-rank tests were used to compare survival differences between groups. Results: A total of 442 patients were enrolled. Mean age was (48.5±12.4) years and 143(32.4%) were female. At (7.6±2.5) years of follow-up, 30 (6.8%) patients met the primary endpoint including 23 SCD and 7 SCD equivalent events, and 36 (8.1%) patients met the secondary endpoint including 33 all-cause death and 3 heart transplant. In multivariate Cox regression, syncope(HR=4.531, 95%CI 2.033-10.099, P<0.001), LGE% (HR=1.075, 95%CI 1.032-1.120, P=0.001) and left ventricular ejection fraction (LVEF) (HR=0.956, 95%CI 0.923-0.991, P=0.013) were independent risk factors for primary endpoint; Age (HR=1.032, 95%CI 1.001-1.064, P=0.046), atrial fibrillation (HR=2.977, 95%CI 1.446-6.131, P=0.003),LGE% (HR=1.075, 95%CI 1.035-1.116, P<0.001) and LVEF (HR=0.968, 95%CI 0.937-1.000, P=0.047) were independent risk factors for secondary endpoint. ROC curve showed the optimal LGE% cut-offs were 5.1% and 5.8% for the prediction of primary and secondary endpoint, respectively. Patients were further divided into LGE%=0, 0Assuntos
Cardiomiopatia Hipertrófica
, Meios de Contraste
, Humanos
, Feminino
, Adulto
, Pessoa de Meia-Idade
, Masculino
, Estudos Retrospectivos
, Volume Sistólico
, Gadolínio
, Função Ventricular Esquerda
, Imageamento por Ressonância Magnética
, Cardiomiopatia Hipertrófica/diagnóstico por imagem
, Morte Súbita Cardíaca
, Medição de Risco
RESUMO
Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Assuntos
COVID-19 , Transtornos do Olfato , Feminino , Humanos , Adolescente , SARS-CoV-2 , Olfato , COVID-19/complicações , Estudos Transversais , Vacinas contra COVID-19 , Incidência , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/etiologia , Distúrbios do Paladar/epidemiologia , Distúrbios do Paladar/etiologia , PrognósticoRESUMO
We propose a lattice-matched Ge/GeSiSn quantum cascade detector (QCD) capable of operating in the longwave infrared. The optical absorption and carrier transport based on intersubband transitions all occur within the L-valley of the conduction band of the group-IV material system using N-doped quantum wells (QWs). The waveguided lattice matched structure can be deposited strain free on top of a Ge buffer grown on Si substrate, and is end-coupled to low-loss on-chip Ge waveguides. We optimized the QCD structure through the analysis of the photoresponsivity and detectivity D*. The QCD operates in photovoltaic mode with narrow spectral response that is peaked anywhere in the 9 to 16 µm range, tunable by design. This work aims to push the optical response of the photodetectors made from the SiGeSn material system to longer wavelengths. The study suggests the QCD response can indeed significantly extend the spectral range beyond that of the photodiodes and photoconductors made from the same group-IV system for a wide variety of applications in imaging, sensing, lidar, and space-and-fiber communications.
RESUMO
Objective: To summarize the different teaching models and their effects in evidence-based medicine at home and abroad by qualitative method and systematic review. Methods: We searched the following databases (from inception to 13 May, 2019): PubMed, Embase, Proquest, Cochrane, Web of Science database and the Chinese databases (CNKI, Wanfang, SinoMed and VIP). To assess data strength and validity, risk of bias assessments were undertaken. Results: A total of 52 literatures were included in this study, including 21 Chinese-language literature and 31 English-language literature. PBL teaching model, mixed teaching model and workshop teaching model were the three teaching models with the largest number of studies in 20 teaching models. Conclusion: The evidence-based medicine teaching effect was closely related to the teaching models, so it is necessary to explore more suitable teaching models for the evidence-based medicine to improve the teaching effects.
Assuntos
Medicina Baseada em Evidências , Modelos Educacionais , China , Medicina Baseada em Evidências/educação , Humanos , Pesquisa QualitativaRESUMO
We report the results of a study that was conducted to investigate the recombination paths of photoexcited charge carriers in GeSn thin films. The charge carrier lifetime was predicted as a function of temperature from a description of photoconductivity transients, assuming co-influence of Shockley-Read-Hall and radiative carrier recombination paths. We identify that dislocations are the source of a band of electronic states with the highest occupied state at E V + (85÷90) meV that acts as Shockley-Read-Hall centers determining the charge carrier lifetime. The photoluminescence (PL) and photoconductivity spectroscopy have been applied to distinguish between the contribution of both band-to-band and dislocation-related electron transitions. The PL band was found to demonstrate a low-energy shift of about 80 ± 20 meV relative to the edge of the photoconductivity spectra in the indirect bandgap GeSn films with dislocations. The role of a different nature deeper acceptor level at E V + (140 ÷ 160) meV in the recombination processes of the GeSn layers with better structural quality and the Sn content higher than 4% was discussed. This detailed understanding of the recombination processes is of critical importance for developing GeSn/Ge-based optoelectronic devices.
RESUMO
Objective: The objective of the study was systematically summarized the current status of the hepatocellular carcinoma (HCC) screening guidelines, and evaluated the HCC screening guidelines according to the authoritative framework of cancer screening guidelines of authoritative institutions, which provided important value for the formulation of HCC screening evidence-based guidelines. Methods: Literature search was conducted in multiple databases from their inception dates to January 3, 2019. In addition, we sought relevant websites further was searched to identify potentially eligible studies. Two reviewers independently screened literature and extracted data. Qualitative description of the basic information, recommendations of HCC screening, source of evidence and update progress of the HCC screening guidelines was conducted. Results: At present, there were no independent HCC screening guidelines worldwide. There were only 17 clinical practice HCC guidelines briefly provided the recommendation of HCC screening. Current HCC screening guidelines only recommended screening for high-risk groups of HCC. All guidelines have identified patients with chronic hepatitis B, hepatitis C and cirrhosis as high-risk groups for HCC. Most of guidelines recommended screening intervals was 6 months. The latest guidelines in Europe and the United States recommended ultrasound for screening HCC. The combination of ultrasound and AFP was recommended in the Asian guidelines. Currently, HCC screening guidelines mainly recommended screening strategies based on factors such as risk of HCC, accuracy of screening modality, screening cost, etc.. The key factors such as screening efficacy and safety have not yet been considered comprehensively. Conclusions: There were no independent HCC screening guidelines worldwide. Only some clinical practice HCC guidelines briefly mentioned HCC screening. Currently, the guidelines only recommend screening for high-risk groups of HCC, with a screening interval of 6 months. There are differences in screening modalities recommended by European, American and Asian guidelines for screening HCC. It is suggested that the relevant institutions should formulate the evidence-based HCC screening guidelines by referring to the theoretical framework of other authoritative other cancer screening guidelines.
Assuntos
Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer , Neoplasias Hepáticas/diagnóstico , Guias de Prática Clínica como Assunto , Ásia , Europa (Continente) , Humanos , Estados UnidosRESUMO
OBJECTIVE: To provide a comprehensive and contemporary overview of the long-term safety outcomes after aortic valve replacements (AVR) with conventional biological heart valve (stented or stentless). METHODS: English databases (Medline, Embase, Web of Science, CENTRAL, and ClinicalTrial.gov) and Chinese databases (CNKI, VIP, WanFang, and SinoMed) were searched systemically from January 1, 2000 to January 26, 2019. Eligible randomized controlled trials, non-randomized clinical trials, cohort studies (retrospective or prospective), and unselected case series were included. Strict screening of the obtained literature was conducted to extract relevant data by two reviewers. Other inclusion criteria were studied reporting on outcomes of AVR with biological valves (stented or stentless), with or without coronary artery bypass grafting (CABG) or valve repair procedure, with mean follow-up length equal to or longer than 5 years. We excluded studies that reported only a specific patient group (e.g., patients with renal failure, or pregnancy), without the report of biological valve type, or with study population size less than 100. The meta-analysis was performed using Stata 14.0 software. RESULTS: In this study, 53 papers (in total 57 study groups) involving 47 803 patients were included. (1) The all-cause mortality was 6.33/100 patient-years (95%CI: 5.85-6.84). Subgroup analysis showed that the mortality rates of porcine and bovine valve prostheses were 5.69/100 patient-years (95%CI: 5.05-6.41) and 7.29/100 patient-years (95%CI: 6.53-8.13), respectively. The all-cause mortality rates for stented and stentless valve were 6.69/100 patient-years (95%CI: 6.12-7.30) and 5.21/100 patient-years (95%CI: 4.43-6.14), respectively. (2) The incidence rate of thromboembolism was 1.16/100 patient-years (95%CI: 0.96-1.40), the incidence rate of permanent pacemaker (PPM) implantation was 1.08/100 patient-years (95%CI: 0.75-1.54), the incidence rate of stroke was 0.74/100 patient-years (95%CI: 0.51-1.06), the incidence rate of structural valve dysfunction (SVD) was 0.73/100 patient-years (95%CI: 0.59-0.91), the incidence rate of major bleeding was 0.52/100 patient-years (95%CI: 0.41-0.65), the incidence rate of endocarditis was 0.38/100 patient-years (95%CI: 0.33-0.44), and the incidence rate of non-structural valve dysfunction (NSVD) was 0.20/100 patient-years (95%CI: 0.13-0.31). The total reoperation rate for biological aortic valve was 0.77/100 patient-years (95%CI: 0.65-0.91), and the SVD related reoperation rate was 0.46/100 patient-years (95%CI: 0.36-0.58). CONCLUSION: The all-cause mortality for conventional biological AVR was 6.33/100 patient-years. Thromboembolism, PPM implantation, reoperation, stroke, and SVD were major long term complications.
Assuntos
Valva Aórtica , Implante de Prótese de Valva Cardíaca , Animais , Bovinos , Humanos , Estudos Prospectivos , Desenho de Prótese , Reoperação , Estudos Retrospectivos , Suínos , Resultado do TratamentoRESUMO
BACKGROUND: This meta-analysis aims to access the efficacy of nasal saline irrigation in the treatment of allergic rhinitis (AR) in adults and children. METHODS: Two authors independently searched databases up to December 2018. Differences in efficacy between saline irrigation and other treatments were compared. Subgroup analyses of discrepancy in effects between children and adults were performed. RESULTS: (1) Saline irrigation vs. no irrigation, in both children and adults groups, saline irrigation showed significant efficacy. (2) Saline+medication vs. medication, in children group, there was no statistical difference of efficacy between saline+medication and medication; in adults group, efficacy of saline+medicine was superior to that of medication. (3) Saline irrigation vs. medication, in children group, there was no statistical difference between efficacy of saline irrigation and medication; in adults group, efficacy of medication was superior to that of saline irrigation. (4) Hypertonic saline vs. isotonic saline, for children, efficacy of hypertonic saline was superior to that of isotonic saline. Additionally, no adults reported adverse events in all trials. Adverse effects were reported during the first nasal irrigation in 20 children, and one child withdrew due to adverse reactions. CONCLUSIONS: Saline irrigation can significantly improve symptoms of AR in children and adults. Saline irrigation can serve as a safe adjunctive treatment to medication of AR in adults. Saline irrigation can be an alternative therapy for children and pregnant women with AR. Efficacy of hypertonic saline may be better than that of isotonic saline in treating AR of children.
Assuntos
Lavagem Nasal/métodos , Rinite Alérgica/terapia , Solução Salina/uso terapêutico , Adulto , Criança , Feminino , Humanos , MasculinoRESUMO
Objective: To establish the key question list for the development of evidence- based guideline in China according to the content and limitation of current evidence-based guidelines around the world. Methods: First, we introduced the evidence-based guidelines in detail which met the criteria based on World Health Organization guideline development handbook and then formulated the draft list of key questions for the development of evidence-based guidelines. At last, the Delphi method was used to determine the list of key questions in developing evidence-based guidelines of colorectal cancer screening. Results: Totally, 34 questionnaires were collected, with experts from clinical and epidemiological fields. The average experts' authority coefficient was 0.81, indicating a high degree of authority. The concentration of opinions on all items in the questionnaire was relatively high, with the full score ratio greater than 75% and the coefficient of variation less than 0.3. The list of key questions on evidence-based guidelines for colorectal cancer screening has been divided into six parts: epidemiological problems, risk classification, screening age, screening tools, implementation and selection of steering group members, which covers the issues that need to be considered in the development of evidence-based colorectal cancer screening guidelines in China. Conclusion: The key question list for evidence-based guideline development in our study can be applied to the development of evidence-based guidelines for colorectal cancer screening in the future, as well as the development of evidence-based guidelines for other cancer screening in China.
Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Prática Clínica Baseada em Evidências , Guias de Prática Clínica como Assunto , China , Técnica Delphi , HumanosRESUMO
Refractory chronic sinusitis is one of the difficult diseases in otolaryngology. Lots of research have been conducted on the pathogenesis and treatment of the refractory chronic sinuses. Many guidelines, including abroad, have provided descriptions and treatment guidelines for the disease, but the definition and diagnostic criteria of refractory chronic sinusitis still need to reach a consensus. Therefore, this article summarizes the latest research status of refractory chronic sinusitis.
Assuntos
Otolaringologia/tendências , Sinusite/diagnóstico , Sinusite/terapia , Doença Crônica , HumanosRESUMO
OBJECTIVE: To systematically review and assess the quality of guidelines on colorectal cancer screening worldwide to provide guidance for the development of high-quality colorectal cancer screening guidelines in mainland China. METHODS: CNKI, WanFang Data, VIP, SinoMed, PubMed, Embase, and Web of Science were systematically searched to identify guidelines on colorectal cancer screening from inception to Jun. 20th, 2018, and so were some websites and major search engines about the development of the guidelines from the existing literature (search date: Aug. 3rd, 2018). Two experienced reviewers independently examined these abstracts and then extracted information, and the Appraisal of Guidelines for Research and Evaluation II (AGREE II) were used to evaluate the methodological quality of these guidelines by four well trained reviewers. RESULTS: In this study, 46 guidelines published from 1994 to 2018 were finally included in our analysis from 10 countries and 5 regions, among which 5 were from mainland China. The quality of these guidelines was relatively high in domain 1 (scope and purpose) and domain 4 (clarity of presentation), and medium in domain 2 (stakeholder involvement). While in the other three domains (domain 3: rigour of development; domain 5: applicability; domain 6: editorial independence), the results were quite different among these guidelines. The quality of evidence-based guidelines (defined by the criteria based on World Health Organization guideline development handbook) was generally higher than that of the common guidelines. Existing guidelines from mainland China were not evidence-based guidelines, which were of low quality. CONCLUSION: The colorectal cancer screening guidelines all over the world are generally large in number, low in quality, different in statements, and so are the guidelines in China. There are no evidence-based guidelines in mainland China, which cannot provide effective guidance for colorectal cancer screening, so we need to pay more attention to the establishment of guidelines with high quality and high credibility for colorectal cancer screening as well as for cancer screening based on the national condition, in order to provide reasonable guidance for practice in public health and improve the health conditions in our society.
Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , China , Neoplasias Colorretais/diagnóstico , HumanosRESUMO
Multi-drug resistance (MDR) of tumor cells attenuates the efficacy of anticancer drugs and has become the main reason for chemotherapy failure. It is indispensable to establish an effective way to reverse multi-drug resistance. Our previous work has shown that down-regulation of the ERK/MAPK signaling pathway activity can reverse the drug-resistance of resistant cells. Further-more, the effect of signal transduction is strongly associated with lipid rafts. The drug-resistance is reversed successfully after lipid rafts are destroyed by heptakis(2, 6-di-O-methyl)-ß-cyclodextrin (MßCD). However, the reversal of the drug-resistance is not associated with down-regulation of the expression of ERK1/2. Cell membrane permeability may increase when lipid rafts are destroyed by MßCD, causing the reversal of drug-resistance due to an increase in accumulation of the drugs in the cytoplasm. To minimize the influence of MßCD on the cell membrane structure, we selected flotillin, a marker protein of lipid rafts, as the target molecule, to further investigate the mechanism of changes in drug resistance after destruction of the lipid rafts. The effect of flotillin on the reversal of the drug resistance was examined using an RNA interference (RNAi) in a retrovirus system in human drug-resistant strains of colorectal cancer cell line HCT-15. The results demonstrate that flotillin-1 downregulation by RNAi (Flot1-RNAi) reduced the drug resistance, caused cell cycle arrest and decreased the expression of ERK1/2; however, apoptosis was not significantly affected. Knockdown of flotillin-2 by RNAi (Flot2-RNAi) had effects similar to those of Flot1-RNAi except that the effects on expression of ERK1/2 and apoptosis were different. Screening of multiple pathways indicated that the PI3K/Akt signaling pathway was closely related. This experiment demonstrates the association between PI3K and drug resistance through the activation of PI3K and suggests that PI3K may play a key role during the development of resistance in CRC. The results reveal that the levels of IRS-1 and PI3K proteins in the Flot1-RNAi and Flot2-RNAi groups were significantly down-regulated. Knockdown of flotillins by RNAi reduced the resistance of HCT-15/ADM cells; the results investigations of the Akt pathway indicate a decrease in resistance after lipid raft destruction. These data confirm that knockdown of flotillin reduces the resistance of HCT-15/ADM cells, and the mechanism may be relevant to the PI3K/Akt pathway. Additionally, flotillin may be used as a potential target for chemotherapy in the treatment of colorectal cancer.
Assuntos
Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos , Microdomínios da Membrana/metabolismo , Proteínas de Membrana/genética , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Técnicas de Silenciamento de Genes , Humanos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Interferência de RNA , Transdução de SinaisRESUMO
This paper summarizes the Risk of Bias of Individual Studies in Systematic Reviews of Health Care Interventions revised by the Agency for Healthcare Research and Quality (AHRQ) and introduces how to use Revman software make risk of bias graph or risk of bias summary. AHRQ tool can be used to evaluate following study designs: RCTs, cohort study, case-control study (including nested case-control), case series study and cross-sectional study. The tool evaluates the risk of bias of individual studies from selection bias, performance bias, attrition bias, detection bias and reporting bias. Each of the bias domains contains different items, and each item is available for the assessment of one or more study designs. It is worth noting that the appropriate items should be selected for evaluation different study designs instead of using all items to directly assess the risk of bias. AHRQ tool can be used to evaluate risk of bias individual studies when systematic reviews of health care interventions is including different study designs. Moreover, the tool items are relatively easy to understand and the assessment process is not complicated. AHRQ recommends the use of high, medium and low risk classification methods to assess the overall risk of bias of individual studies. However, AHRQ gives no recommendations on how to determine the overall bias grade. It is expected that future research will give corresponding recommendations.
Assuntos
Viés , Medicina Baseada em Evidências , Pesquisa sobre Serviços de Saúde , Revisões Sistemáticas como Assunto , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/normasRESUMO
Objective: To compare the tissue morphology and gene expressions of inflammatory and repair-related factors in chronic refractory wound tissue including pressure ulcers and diabetic feet. Methods: During August 2016 to September 2017, 10 samples of prepuce were collected after circumcision of 10 urological patients [all male, aged (38±4) years old] admitted in the First Affiliated Hospital of Nanchang University and included in normal skin group, samples of tissue around the edge of wounds with blood supply were collected from 9 heat or electric burn patients [6 male patients, 3 female patients, aged (51±8) years old], 13 pressure ulcer patients [9 male patients, 4 female patients, aged (51±14) years old] and 10 diabetic foot patients [8 male patients, 2 female patients, aged (61±10) years old] during the operations. The samples were divided into burn wound group (9 samples), pressure ulcer group (13 samples), and diabetic foot group (10 samples). Ten slices were taken from pressure ulcer group and diabetic foot group respectively, and 5 slices in each group were used to observe the tissue morphology and expressions of Ki67 and CD31 of wounds respectively with immunofluorescence method. Ten samples from normal skin group, 9 samples from burn wound group, 13 samples from pressure ulcer group, and 10 samples from diabetic foot group were collected for analysis of mRNA expressions of vascular endothelial growth factor 192 (VEGF192), transforming growth factor ß (TGF-ß), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) , interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor α (TNF-α) by real time fluorescent quantitative reverse transcription polymerase chain reaction. Data were processed with Mann-Whitney U test and Kruskal-Wallis rank-sum test. Results: (1) The expression level of Ki67 in diabetic foot group (390±100) was higher than that of pressure ulcer group (182±14, Z=-2.611, P<0.01). (2) Although there were a large number of vascular endothelial cells (CD31 positive cells) in wounds of diabetic foot group, their distribution was disordered and failed to form intact lumen. There were less vascular endothelial cells in wounds of pressure ulcer group than those of diabetic foot group, but the complete lumen was formed. (3) The mRNA expression levels of VEGF192 in wounds of burn wound group, pressure ulcer group, and diabetic foot group were significantly lower than the level in normal skin group (H=13.72, 30.50, 15.20, P<0.05 or P<0.01), and the level was the lowest in pressure ulcer group. The mRNA expression level of VEGF192 in wounds of pressure ulcer group was significantly lower than that of diabetic foot group (H=15.30, P<0.01). Compared with that of normal skin group, the mRNA expression level of TGF-ß in wounds of burn wound group showed no significant difference (H=-9.50, P>0.05), while the mRNA expression levels of TGF-ß in wounds of pressure ulcer group and diabetic foot group were significantly decreased (H=18.04, 14.50, P<0.01). The mRNA expression level of TGF-ß in wounds of pressure ulcer group was similar to that of diabetic foot group (H=3.54, P>0.05). (4) Compared with those of normal skin group, the mRNA expression levels of VCAM-1 in wounds of burn wound group and pressure ulcer group were significantly increased (H=-22.50, -11.50, P<0.05 or P<0.01), and there was no significant difference in the mRNA expression level of VCAM-1 in wounds of diabetic foot group (H=10.00, P>0.05); the mRNA expression level of ICAM-1 in wounds of burn wound group showed no significant difference (H=-9.50, P>0.05), and the levels of ICAM-1 in wounds of pressure ulcer group and diabetic foot group were significantly decreased (H=16.50, 16.50, P<0.01). The mRNA expression level of VCAM-1 in wounds of pressure ulcer group was significantly higher than that of diabetic foot group (H=-21.50, P<0.01), the mRNA expression level of ICAM-1 in wounds of pressure ulcer group was similar to that of diabetic foot group (H=0, P>0.05). (5) Compared with those of normal skin group, except for the mRNA expression level of IL-1ß in wounds of diabetic foot group showed no significant difference (H=-10.00, P>0.05), the mRNA expression levels of IL-1ß in wounds of burn wound group and pressure ulcer group were significantly increased (H=-32.50, -21.50, P<0.01); the mRNA expression levels of IL-6 were significantly increased in wounds of burn wound group, pressure ulcer group, and diabetic foot group (H=-17.50, -30.50, -11.80, P<0.05 or P<0.01); except for the mRNA expression level of TNF-α in wounds of burn wound group showed no significant difference (H=-9.50, P>0.05), the mRNA expression levels of TNF-α in wounds of pressure ulcer group and diabetic foot group were significantly decreased (H=18.04, 14.50, P<0.01). The mRNA expression levels of IL-1ß and TNF-α in wounds of pressure ulcer group were significantly lower than those of burn wound group (H=11.00, 27.54, P<0.05 or P<0.01), while the mRNA expression level of IL-6 was significantly higher (H=-13.00, P<0.05). The mRNA expression levels of IL-1ß and TNF-α in wounds of diabetic foot group were significantly lower than those of burn wound group (H=22.50, 24.00, P<0.01), while the mRNA expression level of IL-6 showed no significant difference (H=5.70, P>0.05). Conclusions: The phenotypes of diabetic foot and pressure ulcer vary from the expressions levels of proliferating cell nuclear antigen and blood vessels forming ability to the expression levels of growth factors, cell adhesion factors, and inflammatory cytokines.
Assuntos
Citocinas/metabolismo , Expressão Gênica , Interleucina-1beta/genética , Úlcera por Pressão/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Queimaduras , Pé Diabético/metabolismo , Humanos , Interleucina-1beta/metabolismo , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Objective: To evaluate the effect of the application of functional parotid surgery for removal of benign parotid tumors and the prevention of Frey syndrome. Method: One hundred and fifty-six cases with benign tumor were underwent functional regional parotidectomy. All tumors were smaller than 4 cm in diameter. The safe surgical margin was 5 mm when the tumors were less than 2 cm in diameter, while the safety margin was 1 cm for the tumors diameter between 2-4 cm. 156 cases were assigned to two groups(A and B). The absorbable hemostatic sponge was placed between the surface of parotid gland and skin flap after tumor resection in group Aï¼while no sponge was placed in group B. Postoperative followîup was 12-24 months. Result: No compression bandage was performed. No patient had recurrence or salivary fistula. There were 3 cases of temporary facial paralysis, of which 2 cases recovered from the mandibular marginal branch injury within 1 month and 1 case recovered from the facial nerve trunk injury within 6 months. Compared with group B 15.38%(12/78)ï¼the incidence of Frey syndrome was significantly decreased in group A 3.85%ï¼3/78ï¼.χ2=5.728, P<0.05. Conclusion: The removal of benign parotid tumors by functional parotid surgery can effectively preserve the function of residual gland and reduce complication. Intraoperative implantation of absorbable hemostatic sponge between parotid gland and skin flap can reduce the incidence of Frey syndrome.