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BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by intricate genetic and environmental etiology. The objective of this study was to identify robust non-genetic risk factors for AD through an updated umbrella review. METHODS: We conducted a comprehensive search of meta-analyses and systematic reviews on non-genetic risk factors associated with AD in PubMed, Cochrane, Embase, and Ovid Medline up to June 30, 2023. After collecting data, we estimated the summary effect size and their 95% confidence intervals. The degree of heterogeneity between studies was assessed using I2 statistics and a 95% prediction interval was determined. Additionally, we evaluated potential excess significant bias and small study effects within the selected candidate studies. RESULTS: The umbrella review encompassed a total of 53 eligible papers, which included 84 meta-analyses covering various factors such as lifestyle, diet, environmental exposures, comorbidity or infections, drugs, and biomarkers. Based on the evidence classification criteria employed in this study, two factors as convincing evidence (Class I), including rheumatoid arthritis (RA), potentially reduced the risk of AD, but diabetes significantly increased the risk of AD. Furthermore, three factors as highly suggestive evidence (Class II), namely depression, high homocysteine, and low folic acid level, potentially increased the risk of AD. CONCLUSION: Our findings highlight several risk factors associated with AD that warrant consideration as potential targets for intervention. However, it is crucial to prioritize the identified modifiable risk factors, namely rheumatoid arthritis, diabetes, depression, elevated homocysteine levels, and low folic acid levels to effectively address this complex neurodegenerative disorder.
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Doença de Alzheimer , Doença de Alzheimer/genética , Doença de Alzheimer/epidemiologia , Humanos , Fatores de Risco , Artrite Reumatoide/genética , Biomarcadores/sangue , Estilo de VidaRESUMO
Based on first-principles density functional theory and nonequilibrium Green's function, we study the electronic band structures, the electronic transport properties, and the optical absorption of bilayer blue phosphorene nanoribbons (BPNRs). Both bilayer armchair BPNRs (a-BPNRs) and zigzag BPNRs (z-BPNRs) behave as semiconductors in the narrow nanoribbon case and metals in the wide nanoribbon case, sharply different from their monolayer counterparts where the monolayer a-BPNRs (z-BPNRs) are always semiconducting (metallic). This indicates that interlayer couplings or the increasing layer number may induce the switching of the conductivity of the monolayer BPNRs, which is absent in graphene and phosphorene nanoribbons. Furthermore, we explore the edge states of the energy bands near Fermi energy, and find that there are almost no pure edge-state band branches in the bilayer BPNRs, which can be attributed to the interlayer couplings between the edge-states in one layer and the bulk-states in the other. Consequently, the resulting complex band structures cannot be directly analyzed any more in the framework of the two-body coupling picture just according to the simple band structures of the monolayer BPNRs. Finally, we present the current-voltage characteristics and the optical absorption of the bilayer a-BPNRs and z-BPNRs. The influences of the nanoribbon width and the interlayer couplings on the current and the anisotropic optical absorption can be understood based on the complex energy band structures. This research should be an important reference of extending the field of BPNRs from the monolayer to the bilayer case, and deepen the understanding of the difference between the monolayer and bilayer nanoribbons in different materials.
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We systematically investigate the thermoelectric (TE) properties of the Cr-doped blue phosphorene (blue-P) along the armchair and zigzag directions. First, we find the semiconducting band structure of the blue-P will become spin-polarized due to the Cr-doping, and can be seriously changed by the doping concentration. Then we show the Seebeck coefficient, the electronic conductance, the thermal conductance, and the figures of meritZTs are all dependent on the transport directions and doping concentration. However, two pairs of the peaks of the charge and spinZTs can be always observed with the low-height (high-height) pair on the side of the negative (positive) Fermi energy. In addition, at temperature 300 K the extrema of the charge (spin)ZTs of the blue-P along the two directions are kept to be larger than 22 (90) for the different doping concentrations and will be further enhanced at lower temperature. Therefore, we believe the Cr-doped blue-P should be a versatile high-performance TE material which may be used in the fields of the thermorelectrics and spin caloritronics.
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Eletrônica , TemperaturaRESUMO
Objective: To compare oxytocin combined with ergometrine with oxytocin alone in terms of primary prophylaxis for postpartum hemorrhage (PPH) at the time of cesarean section (CS). Methods: This was a multicenter double-blind randomized controlled interventional study comparing ergometrine combined with oxytocin and oxytocin alone administered at CS. From December 2018 to November 2019, a total of 298 parturients were enrolled in 16 hospitals nationwide. They were randomly divided into experimental group (ergometrine intra-myometrial injection following oxytocin intravenously; 148 cases) and control group (oxytocin intra-myometrial injection following oxytocin intravenously; 150 cases) according to 1â¶1 random allocation. The following indexes were compared between the two groups: (1) main index: blood loss 2 hours (h) after delivery; (2) secondary indicators: postpartum blood loss at 6 h and 24 h, placental retention time, incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution; (3) safety indicators: nausea, vomiting, dizziness and other adverse reactions, and blood pressure at each time point of administration. Results: (1) The blood loss at 2 h after delivery in the experimental group [(402±18) ml] was less than that in the control group [(505±18) ml], and the difference was statistically significant (P<0.05). (2) The blood loss at 6 h and 24 h after delivery in the experimental group were less than those in the control group, and the differences were statistically significant (all P<0.05). There were no significant differences between the two groups in the incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution (all P>0.05). (3) Adverse reactions occurred in 2 cases (1.4%, 2/148) in the experimental group and 1 case (0.7%, 1/150) in the control group. There was no significant difference between the two groups (P>0.05). The systolic blood pressure within 2.0 h and diastolic blood pressure within 1.5 h of drug administration in the experimental group were higher than those in the control group, and the differences were statistically significant (P<0.05), but the blood pressure of the two groups were in the normal range. Conclusion: The use of ergometrine injection in CS could reduce the amount of PPH, which is safe and feasible.
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Hemostáticos , Hemorragia Pós-Parto , Gravidez , Feminino , Humanos , Hemorragia Pós-Parto/prevenção & controle , Ergonovina/uso terapêutico , Ocitocina/uso terapêutico , Cesárea , PlacentaRESUMO
Objective: To depict gastric cancer burden trends globally and analyze geographical and socioeconomic disparities among different countries and territories. Methods: We extracted the data from Global Burden of Disease 2019 Database. We conducted the Joinpoint regression and calculated the average annual percent change (AAPC) and corresponding 95% confidence interval (CI) for age-standardized gastric cancer incidence and mortality from 1990 to 2019. Linear regression was performed to measure the association of sociodemographic index (SDI) with each country's gastric cancer incidence and mortality AAPC. We applied the age-period-cohort analysis to assess the cohort effect on gastric cancer incidence and mortality. Results: The AAPCs for gastric cancer age-standardized incidence and mortality rates from 1990 to 2019 were -1.27% (95% CI: -1.43%, -1.11%) and -1.87% (95% CI: -2.01%, -1.72%), respectively. SDI levels were negatively associated with AAPCs, which means that countries with higher SDI had higher AAPC (P<0.001). The decrease of gastric cancer burden in countries with low or medium SDI levels was slower than that globally. The age-period-cohort analysis indicated that countries with higher SDI levels had more apparent decline in birth cohort effects from 1900 to 1999. Conclusions: Countries with different socioeconomic levels have various decreasing rates for gastric cancer incidence and deaths. Countries with higher SDI levels have higher declining rates for gastric cancer burden.
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Carga Global da Doença , Neoplasias Gástricas , Saúde Global , Humanos , Incidência , Anos de Vida Ajustados por Qualidade de Vida , Neoplasias Gástricas/epidemiologiaRESUMO
Objective: To analyze and compare the distribution of the high-risk population of upper gastrointestinal (UGI) cancer and the factors influencing the compliance rate of endoscopic screening in urban China and rural China. Methods: From 2015 to 2017, an epidemiological survey was conducted on residents aged 40-69 in two rural areas (Luoshan county of Henan province, Sheyang county of Jiangsu province) and two urban areas (Changsha city of Hunan province, Harbin city of Heilongjiang province). As a result, high-risk individuals were recommended for endoscopic screening. Chi-square χ(2) test was used to compare the high-risk rate of UGI cancer between urban and rural residents. In addition, the multivariate logistic regression model was used to analyze the factors influencing the compliance rate of endoscopic screening. Results: A total of 48, 310 residents aged 40-69 were enrolled in this study, including 22 870 (47.34%) residents from rural areas and 25 440 (52.66%) residents from urban areas. A total of 23 532 individuals were assessed with a high risk of UGI cancer, with an overall risk rate of 48.71%. A higher proportion of participants with high risk was observed in rural China (56.17%, 12 845/22 870) than in urban China (42.01%, 10 687/25 440). A total of 10 971 high-risk individuals with UGI cancer participated in endoscopic screening, with an overall compliance rate of 46.62% (10 971/23 532), 45.15% (5 799/12 845) in rural China, and 48.40% (5 172/10 687) in urban China. In rural population, the compliance rate of endoscopic screening was higher in those of females, aged 50-69 years, primary school education or above, high income, a family history of UGI cancer, history of gastric and duodenal ulcer, history of reflux esophagitis, and history of superficial gastritis, but lower in smokers (P<0.05). Among the urban population, the compliance rate of endoscopic screening was higher in those aged 40-49 years, uneducated, low income, family history of UGI cancer, history of reflux esophagitis, history of superficial gastritis, but lower in smokers (P<0.05). Conclusions: The proportion of participants with high risk of UGI cancer in rural areas is higher than that of urban areas. The compliance rates of endoscopic screening in urban and rural areas are low, and influencing factors of endoscopic screening exhibit some differences in rural China and urban China.
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Esofagite Péptica , Gastrite , Neoplasias Gastrointestinais , China/epidemiologia , Detecção Precoce de Câncer , Feminino , Neoplasias Gastrointestinais/diagnóstico por imagem , Neoplasias Gastrointestinais/epidemiologia , Humanos , População Rural , População UrbanaRESUMO
Objective: To determine whether insulin resistance is associated with all-cause mortality in subjects without diabetes. Methods: A total of 505 participants without diabetes, 198 with normal glucose tolerance (NGT) and 307 with impaired glucose tolerance (IGT), were recruited from the Daqing Diabetes Study. The participants were followed up for 30 years. They were stratified into three groups (tertiles) according to baseline homeostasis model assessment of insulin resistance(HOMA-IR) levels, as the HOMA-IR 0, the HOMA-IR 1 and the HOMA-IR 2 groups, to assess the predictive effect of insulin resistance on risk of all-cause mortality. Results: During the 30-year follow-up, 52, 56 and 78 participants died across the three HOMA-IR groups, respectively. The corresponding mortality per 1 000 person-years (95%CI) were 12.12 (9.56-15.01), 13.10 (10.46-16.03) and 19.91 (16.73-23.15), respectively. Participants in the HOMA-IR 2 group had a significantly higher risk of death than those in the HOMA-IR 0 group after adjustment of age, sex and smoking status (HR=1.97,95%CI 1.38-2.81, P<0.001). Cox analyses showed that a one standard deviation increase in HOMA-IR was associated with a 22% increase in the mortality after adjustment of potential confounders (HR=1.22, 95%CI 1.08-1.39, P=0.002). Conclusions: Insulin resistance is associated with increased risk of all-cause death in Chinese people without diabetes, suggesting that improving insulin resistance could be beneficial for people without diabetic in reducing risk of long-term all-cause mortality.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Glicemia , Seguimentos , Teste de Tolerância a Glucose , Humanos , InsulinaRESUMO
OBJECTIVE: With this study, we aimed at exploring the regulation mechanism of Potentilla discolor-Euonymus alatus on intestinal flora of T2DM (Type 2 Diabetes Mellitus) rats induced by high-fat diet combined with streptozotocin. MATERIALS AND METHODS: T2DM rats were induced by high-fat diet combined with streptozotocin. There were normal control group, model group, metformin group, high-dose Chinese medicine group and low-dose Chinese medicine group. Each group included 10 rats. Normal control group: normal feeding, no modeling, ordinary feed, and gavage of 0.9% normal saline. Model group: T2DM rats, high-fat diet, and gavage of 0.9% normal saline. Metformin group: T2DM rats, high-fat diet and fed with metformin solution. High-dose Chinese medicine group: T2DM rats, high-fat diet, and gavage of concentrated Chinese medicine at a dose of 6 times the clinical dose. Low-dose Chinese medicine group: T2DM rats, high-fat diet, and gavage of concentrated Chinese medicine at a dose twice the clinical dose. The general situation of T2DM rats was observed, and the changes of intestinal flora were observed with 16SrDNA sequencing. RESULTS: The T2DM rats induced by high-fat diet combined with streptozotocin were molded. After intervention, at the class level, the ratio of γ-proteobacteria was 22.30% in the model group, 11.97% in the metformin group, 3.24% in the high-dose Chinese herbs group and 1.72% in the low-dose Chinese herbs group; the ratio of Erysipelothrix insidiosa was 4.73% in the model group, 4.68% in the metformin group, 3.93% in the high-dose Chinese herbsgroup and 2.92% in the low dose group; the ratio of Lactinobacillus was 2.30% in the model group, 0.01% in the metformin group, 0.00% in the high-dose Chinese herbs group, and 0.00% low-dose Chinese herbs group; at the portal level, the Firmicutes/Bacteroides was 0.88 in the normal control group, 3.40 in the model group, 1.71 in the metformin group, 2.74 in high-dose Chinese medicine group, and 1.34 in low-dose Chinese medicine group; at the genus level, the relative abundance of Lactobacillus in the model group was 3.28%, that of Akkermansia was 1.99%, that of Shigella coli was 22.08%, and that of Vibrio phaseus was 7.67%. All of them were improved after the intervention of metformin and traditional Chinese medicine. CONCLUSIONS: Potentilla discolor-Euonymus Alatus could improve the composition and structure of intestinal flora in T2DM rats and regulate the diversity of intestinal flora. The ratio of Firmicutes/Bacteroidetes was adjusted, mainly to increase the number of Bacteroides; the flora related to intestinal barrier was adjusted, mainly to increase the number of Lactobacillus and Akkermansia bacteria.
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Diabetes Mellitus Tipo 2 , Euonymus , Microbioma Gastrointestinal , Metformina , Potentilla , Ratos , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Potentilla/química , Estreptozocina , Solução Salina , Metformina/farmacologiaRESUMO
ABSTRACT: Objective To detect the uncontrolled new psychoactive tryptamines involved in drug-related cases with high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Methods White and brown powder obtained in actual cases were extracted and analyzed by gas chromatography-quadrupole time-of-flight mass spectrometry ï¼GC-QTOF-MSï¼, ultra-high performance liquid chromatography-linear ion trap quadrupole-orbitrap mass spectrometry ï¼UPLC-LTQ-Orbitrap MSï¼ and 1H-nuclear magnetic resonance spectroscopy ï¼1H-NMRï¼. Results After detection by GC-QTOF-MS, the components of white powder showed main characteristic fragment ion peaks at m/z 218.141 0 ï¼molecular ion peakï¼, 72.080 6 ï¼base peakï¼, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 219.149 4. The main ions in the secondary mass spectrum under the collision-induced dissociation ï¼CIDï¼ mode were m/z 160.076 3 and 72.080 8. After detection by GC-QTOF-MS, the components of brown powder showed main characteristic fragment ion peaks at m/z 246.135 7 ï¼molecular ion peakï¼, 58.065 1 ï¼base peakï¼, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 247.145 0. The main ions in the secondary mass spectrum under CID mode were m/z 202.087 1, 160.076 3 and 134.060 5. NIST 17 library retrieval and 1H-NMR confirmed that the white powder and brown powder contained new psychoactive tryptamines 4-OH-MET and 4-AcO-DMT, respectively. Conclusion GC-QTOF-MS, UPLC-LTQ-Orbitrap MS and 1H-NMR can be used together to identify unknown new psychoactive substances.
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Triptaminas , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Espectroscopia de Ressonância Magnética , Espectrometria de MassasRESUMO
Objective: To systematically evaluate the methodological quality of screening guidelines for upper gastrointestinal cancer (including esophageal cancer and gastric cancer) both at home and abroad, and provide reference for the update of upper gastrointestinal cancer screening guidelines in China. Methods: Original articles and grey literature published as of 31th Aug 2020 were retrieved using Chinese databases (CNKI, Wanfang, China Biomedical Literature Database and China Guideline Clearinghouse), PubMed, The Cochrane Library and Embase, as well as those from International Agency for Research on Cancer and the International Guide Collaboration Network. The inclusion criteria were being independent guidelines/recommendation documents for upper gastrointestinal cancer screening and meeting the definition of the institute of Medicine, USA. The exclusion criteria were being guideline abstracts, interpretation and evaluation literature, duplicate publications, updated original guidelines, and clinical treatment or practice guidelines for esophageal or gastric cancer. Appraisal of Guidelines for Research and Evaluation (AGREE â ¡) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) were used to compare and evaluate the quality and reporting standard of esophageal or gastric cancer screening guidelines. Results: A total of 6 esophageal cancer screening guidelines and 5 gastric cancer screening guidelines were included. The results of the AGREE â ¡ quality evaluation showed that the overall quality of eleven guidelines varied, including two guidelines recommended for "A", one for "B", five for "C" and three for "D". The guidelines had higher scores in the areas of scope and purpose, and clarity. The esophageal cancer screening guidelines had different scores in the areas of rigor and independence. The gastric cancer screening guidelines generally had low scores in the areas of participants and application. The RIGHT evaluation results showed that the quality of eleven guidelines should be improved. The six items with poor report quality were background, evidence, recommendations, review and quality assurance, funding and conflict of interest statement and management and others. Conclusion: The quality of the included upper gastrointestinal cancer screening guidelines is general, and the standardization needs to be strengthened.
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Detecção Precoce de Câncer , Guias de Prática Clínica como Assunto , Neoplasias Gástricas , China , Consenso , Humanos , Padrões de Referência , Neoplasias Gástricas/diagnósticoRESUMO
ABSTRACT: Objective To establish a method for determination of the azide ions in blood by gas chromatography-mass spectrometry ï¼GC-MSï¼ following pentafluorobenzyl derivatization. Methods A blood sample of 0.2 mL was placed into a 10 mL glass test tube, and the internal standard sodium cyanide, derivatization reagent pentafluorobenzyl bromide and catalyst tetradecyl benzyl dimethyl ammonium chloride were added in turn. After vortex mixing, the mixture was heated with low-power microwave for 3 min. After centrifugation, the organic phase was taken for GC-MS analysis. Results The azide ions in blood had a good linear relationship in the mass concentration range of 0.5 to 20 µg/mL. The lowest detection limit was 0.25 µg/mL and the relative recovery was 91.36%-94.58%. The method was successfully applied to a case of death from sodium azide poisoning. The mass concentration of azide ions in the blood of the dead was 11.11 µg/mL. Conclusion The method developed in this paper has strong specificity and is easy to operate, which is suitable for the rapid detection of azide ions in blood.
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Azidas , Cromatografia Gasosa-Espectrometria de Massas , Humanos , ÍonsRESUMO
Prostate cancer is the second most common malignancy in men worldwide. An increasing trend for prostate cancer incidence was observed in China. Enormous studies have been conducted to investigate the association between dietary factors and prostate cancer, however conflicted results were obtained. Red meat, processed meat, and dairy products consumption were reported to be associated with the increased prostate cancer risk, while tomatoes, soybeans and green tea might reduce the risk of prostate cancer occurance. However, no consensus could be reached without strong evidence. Furthermore, further studies are needed to investigate the association between vitamin and mineral supplements and prostate cancer risk. Some studies reported that men with higher dietary inflammatory index scores increased prostate cancer risk. There may be a long susceptible period when dietary factors affect prostate cancer risk, which poses challenges for collecting exposure and the follow-up. Measure bias and detection bias are the main reasons which impair the authenticity of studies on the relationship of dietary factors and prostate cancer risk. Researchers should apply various methods to measure participants' dietary consumption levels and ascertain essential outcomes, such as prostate cancer death. This article reviews updated epidemiological evidences on the association of dietary factors and prostate cancer, aims to benefit future nutritional epidemiology studies focus on the prostate cancer prevention.
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Laticínios , Neoplasias da Próstata , China , Humanos , Masculino , Estudos Prospectivos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/etiologia , Fatores de RiscoRESUMO
Objective: To systematically review the quality of clinical practice guidelines for prostate cancer screening to serve as a reference for developing prostate cancer screening guidelines in China. Methods: We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and SinoMed with the term "prostate cancer" "prostate carcinoma" "prostate tumor" "screening" "early detection" "guideline" "recommendation" as keywords. The Appraisal of Guidelines for Research & Evaluation (AGREE) â ¡ instrument and Reporting Items for Practice Guidelines in Healthcare (RIGHT) were used for critical appraisal. Results: A total of thirteen guidelines were included in this review. Evaluated by the AGREE â ¡ instrument, ten were considered as A level. Two guidelines scored B level, and one was considered C level. Lowest mean domain scores were for stakeholder involvement (52.1%) and applicability (34.0%). Using the RIGHT checklist, we found that the low reporting quality of the thirteen guidelines could be attributable to incomplete disclosure of evidence (64.6%), funding, declaration and management of interest (44.2%), or other information (46.2%). Conclusions: No guidelines for prostate cancer screening was developed in China. The methodological quality of the guidelines in prostate cancer screening was good, which set a tone for the development of Chinese guidelines. However, all guidelines showed poor reporting quality.
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Detecção Precoce de Câncer , Saúde Global , Guias de Prática Clínica como Assunto , Neoplasias da Próstata , China , Humanos , Masculino , Guias de Prática Clínica como Assunto/normas , Neoplasias da Próstata/diagnósticoRESUMO
Objective: To systematically assess the quality of guidelines/consensus on live cancer screening globally and provide references for the formulation of evidence-based guideline on liver cancer screening in China. Methods: PubMed, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, SinoMed, and other related guideline development institutions were searched to identify guidelines on live cancer screening before June 30, 2020. Two experienced reviewers screened literature and extracted data independently. The Appraisal of Guidelines for Research & Evaluation â ¡(AGREE â ¡) and Reporting Items for Practice Guideline in Healthcare (RIGHT) were used to evaluate the quality of guidelines. Results: A total of 19 guidelines/consensus issued between 2003 and 2019 were included in this study. The quality of these guidelines was high according to AGREE â ¡, nine of which were recommended as level A, and the other five were graded as level B. Each guidance scored higher in scope and purpose, stakeholder involvement, and clarity of presentation. The reporting quality of basic information with 56.1% reporting rate was the highest based on RIGHT. The reporting quality of background (37.5%) and recommendations (39.8%) were acceptable. However, evidence (35.8%), review and quality assurance (18.4%), funding and declaration and management of interests (22.4%) and other information (21.0%) still need to be improved. Conclusions: Although the quality of screening guidelines for liver cancer is acceptable, the evidence, review and quality assurance, and funding and declaration and management of interests still need to be strengthened. There is still a lack of solely evidence-based medical screening guidelines for liver cancer in China.
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Detecção Precoce de Câncer , Saúde Global , Neoplasias Hepáticas , Guias de Prática Clínica como Assunto , China , Consenso , Humanos , Neoplasias Hepáticas/diagnóstico , Guias de Prática Clínica como Assunto/normasRESUMO
Toxoplasma gondii infects almost all warm-blooded animals and negatively affects the health of a wide range of these animals, including humans. Protein phosphatase 2C (PP2C) is a T. gondii protein secreted by rhoptry organelles during host cell invasion. However, very little is known about whether this protein can induce protective immunity against T. gondii. In this study, bioinformatics analysis of PP2C revealed some useful information in the context of anti-toxoplasmosis treatments and vaccine research. In addition, the PP2C gene was amplified, and a eukaryotic expression vector (pEGFP-PP2C) was successfully constructed to express PP2C. Finally, the constructed pEGFP-PP2C was injected into mice to evaluate whether it could induce immunoprotection. Compared with the control groups, we found that immunizations with the pEGFP-PP2C plasmid could elicit specific IgG antibodies and cytokines against T. gondii infection. The survival of mice immunized with the pEGFP-PP2C plasmid was significantly prolonged compared with that of the control group mice. Based on the ability of pEGFP-PP2C to induce specific immune responses against T. gondii, we propose that PP2C merits consideration as a potential vaccine candidate against toxoplasmosis.
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Proteína Fosfatase 2C/imunologia , Vacinas Protozoárias/normas , Toxoplasma/imunologia , Toxoplasmose/prevenção & controle , Vacinas de DNA/normas , Animais , Anticorpos Antiprotozoários/biossíntese , Anticorpos Antiprotozoários/sangue , Linfócitos B/química , Linfócitos B/imunologia , Biologia Computacional , Citocinas/biossíntese , Epitopos/análise , Epitopos/química , Feminino , Células HEK293 , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Concentração Inibidora 50 , Camundongos , Camundongos Endogâmicos BALB C , Proteína Fosfatase 2C/química , Proteína Fosfatase 2C/metabolismo , Vacinas Protozoárias/imunologia , Baço/imunologia , Linfócitos T/química , Linfócitos T/imunologia , Vacinas de DNA/imunologiaRESUMO
OBJECTIVE: Chemoresistance is the leading cause of recurrence in non-small cell lung cancer (NSCLC). The long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) inhibits the tumorigenesis of various cancers. However, the regulatory function of CASC2 on the chemoresistance of NSCLC remains unclear. PATIENTS AND METHODS: The levels of CASC2 and miR-18a in cisplatin (DDP)-resistant NSCLC tissues and cell lines were evaluated by quantitative Polymerase Chain Reaction (qPCR). The role of low CASC2 levels on overall survival in patients with NSCLC was tested using the log-rank test. The Chi-squared test was used to assess the relation between CASC2 expression and clinicopathological features of NSCLC patients. Cell Counting Kit-8 (CCK-8) assays tested the cell proliferation of cisplatin-resistant NSCLC cells (H226/DDP and A549/DDP). The underlying regulatory mechanism between CASC2 and miR-18a or miR-18a and interferon regulatory factor 2 (IRF-2) was predicted by bioinformatics and verified by a Dual-Luciferase reporter assay, RNA transfection, qPCR, and Western blotting. Chromatin immunoprecipitation (ChIP) assay was done to exam the relation between E74 like factor 1 (ELF1) and CASC2 gene. Mice xenografts were applied to exam the function of CASC2 on chemosensitivity of cisplatin of NSCLC cells in vivo. RESULTS: Low CASC2 expression is more likely to present in patients with advanced TNM stage (IV), cisplatin-resistance, and poor overall survival. The expression of CASC2 sharply decreased in cisplatin-resistant NSCLC tissues and cell lines (H226/DDP and A549/DDP). CASC2 overexpression strongly inhibited proliferation, migration, and invasion of cisplatin-resistant NSCLC cells (H226/DDP and A549/DDP) in vitro and inhibited tumor growth in vivo. Besides, CASC2 repressed miR-18a function by binding to the complementary sites of miR-18a as competing endogenous RNAs (ceRNAs). MiR-18a released by the declining expression of CASC2 reduced the protein concentration of IRF-2 in NSCLC cells. Furthermore, the transcription factor ELF1 was found to be promotor of CASC2 and increased its levels in cisplatin-resistant NSCLC cells. CONCLUSIONS: IRF-2 expression mediated by the ELF1/CASC2/miR-18a axis is markedly associated with the proliferation, migration, and invasion of cisplatin-resistant NSCLC, resulting in inferior survival. These findings suggest that this regulatory axis may serve as a novel therapeutic target in NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fator Regulador 2 de Interferon/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Fator Regulador 2 de Interferon/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
ABSTRACT: From January 15 to March 3, 2020, seven editions of the guidelines for the diagnosis and treatment of COVID-19 have been issued successively by the National Health Commission of the People's Republic of China, and the guidelines' name was changed from Guidelines for Diagnosis and Treatment of Novel Coronavirus Pneumonia to Diagnosis and Treatment for COVID-19. It optimized and perfected the etiology, clinical manifestations and types, diagnostic procedures and specific treatment measures of the disease, so that the clinical management of the cases was more scientific. In the revision process of guidelines for diagnosis and treatment, forensic medicine experts have also made some positive suggestions on clinical diagnosis and treatment. Especially regarding the pathological changes of COVID-19, they have repeatedly called for rapid autopsy at different levels. With the support, understanding and cooperation of all parties, pathological examination of more than ten cases of the remains were carried out, which made an important contribution to the understanding of the clinical characteristics and pathological characteristics of the disease and the improvement of treatment plans.
Assuntos
COVID-19 , China , Protocolos Clínicos , Medicina Legal , Humanos , SARS-CoV-2RESUMO
ABSTRACT: Objective To identify tiletamine, zolazepam and their metabolites in samples from drug facilitated sexual assault by gas chromatography-quadrupole time of flight mass spectrometry ï¼GC-QTOF-MSï¼. Methods Urine samples of victims were collected, and detected by GC-QTOF-MS after liquid-liquid extraction and concentration. The molecular formula of fragments ions was identified by determination of accurate mass numbers, to detect related substances. Results Tiletamine, zolazepam, three metabolites of tiletamine and two metabolites of zolazepam were identified in urine samples from actual cases. Conclusion GC-QTOF-MS provides abundant and accurate information of fragment ions mass numbers, which can be used for qualitative identification of tiletamine, zolazepam and their metabolites in drug facilitated sexual assault.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Toxicologia Forense/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Delitos Sexuais , Espectrometria de Massas em Tandem/métodos , Tiletamina/análise , Zolazepam/análise , Humanos , Tiletamina/sangue , Zolazepam/sangueRESUMO
Objective: To deeply investigate the gene expression profiles of esophageal squamous cell carcinoma (ESCC) and the relationship of gene expression levels with prognosis from The Cancer Genome Atlas (TCGA) database. Methods: RNA-seq V2 data of 11 normal samples and 81 esophageal squamous cell carcinoma patients, and their corresponding clinical data were downloaded from The Cancer Genome Atlas database. Differentially expressed genes between normal and tumor samples were identified by using edgeR package. Gene function enrichment analyses of differentially expressed genes were conducted. A protein-protein interaction network based on differentially expressed genes was constructed by using STRING database and the hub genes were identified based on the created gene co-expression network. In addition, survival analysis was performed. Results: Totally, 2 788 genes were identified as differential expression. Among these, 1 168 genes were up-regulated and 1 620 genes were down-regulated in tumor cases compared with normal samples. Up-regulated genes were enriched in cell cycle, DNA replication and mismatch repair pathways, while down-regulated genes were enriched in metabolic pathways. 707 genes and their 3 428 interactions were identified by protein-protein interaction analysis. Genes with copy number amplifications were considered to interact with other crucial genes. 10 co-expression modules were identified based on the gene co-expression network analysis and the ribosomal protein genes were illustrated to be correlated with tumor locations of ESCC patients (P=0.003). The 3-years survival rates of high and low expression of TNFRSF10B groups were 82.5% and 15.1%, respectively. Similarly, the 3-years survival rates of high and low expression of DDX18 groups were 82.4% and 15.2%, respectively. The survival differences stratified by these two genes were statistically significant (both P<0.1). Conclusions: The analysis results of TCGA database showed that ribosomal protein genes are correlated with tumor locations of ESCC patients. Low expressions of TNFRSF10B and DDX18 are associated with poor prognose of ESCC patients. Consequently, TNFRSF10B and DDX18 may serve as predictive markers for ESCC patients.