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Colloidal quantum dots (QDs) are shown to be effective as light-harvesting sensitizers of metal oxide semiconductor (MOS) photoelectrodes for photoelectrochemical (PEC) hydrogen (H2) generation. The CdSe/CdS core/shell architecture is widely studied due to their tunable absorption range and band alignment via engineering the size of each composition, leading to efficient carrier separation/transfer with proper core/shell band types. However, until now the effect of core size on the PEC performance along with tailoring the core/shell band alignment is not well understood. Here, by regulating four types of CdSe/CdS core/shell QDs with different core sizes (diameter of 2.8, 3.1, 3.5, and 4.8 nm) while the thickness of CdS shell remains the same (thickness of 2.0 ± 0.1 nm), the Type II, Quasi-Type II, and Type I core/shell architecture are successfully formed. Among these, the optimized CdSe/CdS/TiO2 photoelectrode with core size of 3.5 nm can achieve the saturated photocurrent density (Jph) of 17.4 mA cm-2 under standard one sun irradiation. When such cores are further optimized by capping alloyed shells, the Jph can reach values of 22 mA cm2 which is among the best-performed electrodes based on colloidal QDs.
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BACKGROUND: Our study aimed to compare the predictive performance of different hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B patients receiving entecavir or tenofovir, including discrimination, calibration, negative predictive value (NPV) in low-risk, and proportion of low-risk. METHODS: We conducted a systematic literature research in PubMed, EMbase, the Cochrane Library, and Web of Science before January 13, 2022. The predictive performance was assessed by area under receiver operating characteristic curve (AUROC), calibration index, negative predictive value, and the proportion in low-risk. Subgroup and meta-regression analyses of discrimination and calibration were conducted. Sensitivity analysis was conducted to validate the stability of the results. RESULTS: We identified ten prediction models in 23 studies. The pooled 3-, 5-, and 10-year AUROC varied from 0.72 to 0.84, 0.74 to 0.83, and 0.76 to 0.86, respectively. REAL-B, AASL-HCC, and HCC-RESCUE achieved the best discrimination. HCC-RESCUE, PAGE-B, and mPAGE-B overestimated HCC development, whereas mREACH-B, AASL-HCC, REAL-B, CAMD, CAGE-B, SAGE-B, and aMAP underestimated it. All models were able to identify people with a low risk of HCC accurately. HCC-RESCUE and aMAP recognized over half of the population as low-risk. Subgroup analysis and sensitivity analysis showed similar results. CONCLUSION: Considering the predictive performance of all four aspects, we suggest that HCC-RESCUE was the best model to utilize in clinical practice, especially in primary care and low-income areas. To confirm our findings, further validation studies with the above four components were required.
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Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Tenofovir/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Neoplasias Hepáticas/epidemiologia , Antivirais/uso terapêuticoRESUMO
A novel method for the synthesis of formamides through the decarboxylative N-formylation of amines with glyoxylic acid has been developed. This transformation provides an efficient protocol for the synthesis of various formamides with moderate to excellent yields, and it can accommodate a wide range of functional groups under metal free and base free conditions. In addition, the large-scale experiments and high chemoselectivity have shown great potential application of this strategy.
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Methods: We retrospectively screened individuals with serum Cp ≥ 140 mg/L from 1032 WD patients who were hospitalised for the first time. Logistic regression analyses were performed in a case-control study between the WD cohort and another liver disease cohort to explore the independent risk factors for WD diagnosis and establish a regression model to identify them. The follow-up medical records of the WD cohort were subjected to mixed-effects model analysis in a longitudinal study to discover factors associated with Cp normalisation. Results: Eighty-six WD patients and their 353 medical records and another 98 non-WD liver disease patients were included in the present study. Cp normalisation was significantly associated with the copper burden and liver function indexes, such as urinary copper, γ-glutamyltransferase, and albumin (p ≤ 0.001). Logistic regression analysis showed that age and serum creatinine (p ≤ 0.001) were independent risk factors associated with WD. The AUC value of the regression model in the total cohort was 0.926 (p ≤ 0.001). At a cutoff value of ≥0.617 and ≥-1, the positive and negative predictive values were both 90.8% for WD. Conclusion: Increased serum Cp in WD patients is related to excessive copper burden and hepatic injury, and common tests can effectively distinguish WD patients from other liver injury patients.
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Degeneração Hepatolenticular , Humanos , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/complicações , Ceruloplasmina/análise , Ceruloplasmina/metabolismo , Cobre/metabolismo , Creatinina , Estudos Retrospectivos , Estudos de Casos e Controles , Estudos LongitudinaisRESUMO
BACKGROUND: This study aimed to estimate hepatitis B incidence and chronicity risk in rural adults in China under the background of eliminating viral hepatitis. METHODS: Hepatitis B surface antigen (HBsAg) screening was conducted every 2 years in demonstration areas since 2011. Individuals with baseline HBsAg-negative were included. Incidence was calculated as the number of HBsAg-positive cases divided by the total person-times. HBsAg-positive individuals were followed up to study the persistent infection (> 6 months), chronic infection (> 12 months), and recovery with hepatitis B surface antibody (anti-HBs). The chi-square test and cox proportional regression analysis were performed. RESULTS: There were 8,942 incident cases over 2,138,532 person-years, yielding an average incidence of 0.42 per 100 person-years. HBV incidence decreased rapidly in both genders and all age groups and then kept stable. Male gender, low population density, low gross domestic product per capita, and islanders were associated with higher incidence. Of the positive cases, 4,989 (55.8%) patients were followed up. The persistent infection, chronic infection, and recovery with anti-HBs rates were 32.3%, 31.0%, and 31.4%, respectively. Persistent or chronic infection was more common in younger adults and males, while seroconversion had no concern with gender or age. CONCLUSIONS: HBV incidence in adult rural residents was decreasing and stayed low. The chronicity rate was relatively high and protective antibodies were induced in only one third. The importance of population-based screening and vaccination for susceptible individuals should be addressed.
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Antígenos de Superfície da Hepatite B , Hepatite B , Humanos , Adulto , Masculino , Feminino , Seguimentos , Infecção Persistente , Fatores de Risco , Incidência , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B , China/epidemiologia , Vírus da Hepatite BRESUMO
BACKGROUND: Human papillomavirus (HPV) vaccination could prevent cervical and other HPV-associated cancers attributable to vaccine-associated HPV types. However, HPV vaccination coverage among women aged 9-18 years old is low in China. Common barriers include poor financial affordability, minimal public engagement, and low confidence in domestically produced HPV vaccines. Pay-it-forward offers an individual a free or subsidized service then an opportunity to voluntarily donate and/or create a postcard message to support future people. This study aims to assess the effectiveness of pay-it-forward as compared to standard-of-care self-paid vaccination to improve HPV vaccine uptake among adolescent girls aged 15-18 years, who are left out in the current pilot free HPV vaccination task force in some parts of China. METHODS: This is a two-arm randomized controlled trial in Chengdu, China. Eligible adolescent girls (via caregivers) will be randomly selected and recruited through four community health centers (one in the most developed urban areas, one in higher middle-income and one in lower middle-income suburban areas, and one in the least developed rural areas) using the resident registration list. A total of 320 participants will be randomized into two study arms (user-paid versus pay-it-forward vaccination) in a 1:1 ratio. The intervention assignment will be blinded to recruiters and participants using envelop concealment until the research assistants open the envelop to determine which treatment to deliver to each individual. The primary outcome of the study will be HPV vaccine uptake by administrative data. Secondary outcomes include costs, vaccine hesitancy, and the completion rates of the 3-dose HPV vaccination series. DISCUSSION: This study will investigate an innovative pay-it-forward strategy's effectiveness and economic costs to improve HPV vaccination among 15-18-year-old adolescent girls. Study findings will have implications for increasing HPV vaccine uptake in places where HPV vaccines are provided for a fee. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR2200055542. Registered on 11 January 2022.
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Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Adolescente , Criança , Infecções por Papillomavirus/prevenção & controle , Hesitação Vacinal , Vacinação/métodos , China , Neoplasias do Colo do Útero/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Recent studies have revealed that the combination therapy of atorvastatin (ATV) with naringenin (NG) can offer meaningful benefits in the treatment of hypercholesterolemia, while decreasing adverse side effects. To investigate whether there are pharmacokinetic interactions among ATV, its metabolite 2-hydroxy atorvastatin (2-ATV), and NG, in the current study, we developed and validated a simple, rapid, and specific UPLC-MS/MS method to simultaneously determine the concentrations of these analytes in the rat plasma. Sample preparation was performed using simple protein precipitation. Chromatographic analysis was carried out on an Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 100 mm) using gradient elution mode, and these three analytes were detected using a Xevo® TQD triple quadrupole tandem mass spectrometer, in the positive ion electrospray ionization interface. The developed method showed good linearity over the following concentrations in rat plasma samples: 3-1200 ng/ml (r = 0.9965) for ATV, 1.5-600 ng/ml (r = 0.9934) for 2-ATV, and 3-1200 ng/ml (r = 0.9964) for NG. The assays were validated and satisfied the acceptance criteria recommended by U.S. Food and Drug Administration guidelines. Upon successful application of the method to a pharmacokinetic interaction study, the results indicated that NG significantly enhanced the bioavailability of ATV and 2-ATV.
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Espectrometria de Massas em Tandem , Ratos , Animais , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Atorvastatina/farmacocinética , Cromatografia Líquida/métodos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The monitoring of intracranial pressure (ICP) and detection of increased ICP are crucial because such increases may cause secondary brain injury and a poor prognosis. Although numerous ultrasound parameters, including optic nerve sheath diameter (ONSD), width of the crural cistern (WCC), and the flow velocities of the central retinal artery and middle cerebral artery, can be measured in patients after hemicraniectomy, researchers have yet to determine which of these is better for evaluating ICP. This study aimed to analyze the correlation between ICP and ultrasound parameters and investigate the best noninvasive estimator of ICP. METHODS: This observational study enrolled 50 patients with brain injury after hemicraniectomy from January 2021 to December 2021. All patients underwent invasive ICP monitoring with microsensor, transcranial, and ocular ultrasound postoperatively. We measured the ONSD including the dura mater (ONSDI), the ONSD excluding the dura mater, the optic nerve diameter (OND), the eyeball transverse diameter (ETD), the WCC, and the flow velocities in the central retinal artery and middle cerebral artery. Then, we calculated the ONSDI-OND (the difference between ONSDI and OND) and ONSDI/ETD (the ratio of ONSDI to ETD). Patients were divided into a normal ICP group (n = 35) and an increased ICP group (≥ 20 mm Hg, n = 15) according to the ICP measurements. Correlations were then assessed between the values of the ultrasound parameters and ICP. RESULTS: The ONSDI, ONSDI-OND, and ONSDI/ETD were positively associated with ICP (r = 0.455, 0.482, 0.423 and p = 0.001, < 0.001, 0.002, respectively), whereas the WCC was negatively associated with ICP (r = - 0.586, p < 0.001). The WCC showed the highest predictive power for increased ICP (area under the receiver operating characteristic curve [AUC] = 0.904), whereas the ONSDI-OND and ONSDI also presented with acceptable predictive power among the ONSD-related parameters (AUC = 0.831, 0.803, respectively). The cutoff values for increased ICP prediction for ONSDI, ONSDI-OND, and WCC were 6.29, 3.03, and 3.68 mm, respectively. The AUC of the combination of ONSDI-OND and WCC was 0.952 (95% confidence interval 0.896-1.0, p < 0.001). CONCLUSIONS: The ONSDI, ONSDI-OND, and WCC were correlated with ICP and had acceptable accuracy levels in estimating ICP in patients after hemicraniectomy. Furthermore, WCC showed a higher diagnostic value than ONSD-related parameters, and the combination of ONSDI-OND and WCC was a satisfactory predictor of increased ICP.
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Lesões Encefálicas , Craniectomia Descompressiva , Hipertensão Intracraniana , Humanos , Pressão Intracraniana/fisiologia , Hipertensão Intracraniana/diagnóstico por imagem , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/cirurgia , Ultrassonografia/métodos , Lesões Encefálicas/complicações , Nervo Óptico/diagnóstico por imagemRESUMO
BACKGROUND: Taxus is a rare gymnosperm plant that is the sole producer of the anticancer drug paclitaxel. The growth and development of Taxus is affected by environmental factors such as light. However, little is known about how light conditions affect growth and metabolic processes, especially paclitaxel biosynthesis. RESULTS: In this study, we applied three different light conditions to Taxus chinensis young saplings and investigated the physiological response and gene expression. Our observations showed that exposure to high light led to oxidative stress, caused photoinhibition, and damaged the photosynthetic systems in T. chinensis. The paclitaxel content in T. chinensis leaves was significantly decreased after the light intensity increased. Transcriptomic analysis revealed that numerous genes involved in paclitaxel biosynthesis and phenylpropanoid metabolic pathways were downregulated under high light. We also analyzed the expression of JA signaling genes, bHLH, MYB, AP2/ERF transcription factors, and the CYP450 families that are potentially related to paclitaxel biosynthesis. We found that several CYP450s, MYB and AP2/ERF genes were induced by high light. These genes may play an important role in tolerance to excessive light or heat stress in T. chinensis. CONCLUSIONS: Our study elucidates the molecular mechanism of the effects of light conditions on the growth and development of T. chinensis and paclitaxel biosynthesis, thus facilitating the artificial regeneration of Taxus and enhancing paclitaxel production.
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Taxus , Taxus/genética , Perfilação da Expressão Gênica , Fotossíntese/genética , Cycadopsida , Luz , PaclitaxelRESUMO
BACKGROUND: Gastric cancer (GC) is common in East Asia, yet its molecular and pathogenic mechanisms remain unclear. Circular RNAs (circRNAs) are differentially expressed in GC and may be promising biomarkers. Here, we investigated the role and regulatory mechanism of circTMC5 in GC. METHODS: CircTMC5 expression was detected in human GC and adjacent tissues using microarray assays and qRT-PCR, while the clinicopathological characteristics of patients with GC were used to assess its diagnostic and prognostic value. The circTMC5/miR-361-3p/RABL6 axis was examined in vitro and vivo, and the immune roles of RABL6 were evaluated using bioinformatics analyses and immunohistochemistry (IHC). RESULTS: CircTMC5 was highly expressed in GC tissues, plasma, and cell lines, and was closely related to histological grade, pathological stage, and T classification in patients with GC. CircTMC5 expression was also an independent prognostic factor for GC and its combined detection with carcinoembryonic antigen may improve GC diagnosis. Low circTMC5 expression correlated with good prognosis, inhibited GC cell proliferation, and promoted apoptosis. Mechanistically, circTMC5 overexpression promoted GC cell proliferation, invasion, and metastasis but inhibited apoptosis by sponging miR-361-3p and up-regulating RABL6 in vitro and vivo, whereas miR-361-3p up-regulation had the opposite effects. RABL6 was highly expressed in GC and was involved in immune regulation and infiltration in GC. CONCLUSIONS: CircTMC5 promotes GC and sponges miR-361-3p to up-regulate RABL6 expression, thus may have diagnostic and prognostic value in GC. RABL6 also displays therapeutic promise due to its role in the immune regulation of GC.
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MicroRNAs , Neoplasias Gástricas , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Gástricas/patologia , Proteínas rasRESUMO
Ulcerative colitis (UC) is a disease characterized by inflammation and disruption of the intestinal epithelial barrier. Necroptosis plays a critical role in disease progression. Indole-3-carbinol (I3C), a natural dietary agonist of aryl hydrocarbon receptor (AHR), has shown alleviating effects on UC. However, its mechanisms of action have not been comprehensively elucidated. Therefore, we aimed at investigating the protective role of I3C in DSS-induced colitis mice models. I3C significantly ameliorated body weight loss, colon length shortening and colonic pathological damage in colitis mice, reduced disease activity index (DAI) and histological (HI) scores, as well as alleviated colonic necroptosis and inflammation. In vitro, I3C attenuated necroptosis and inflammation of colonoids and NCM460 cells. AHR, activated by I3C, inhibits activation of receptor-interacting protein kinase 1 (RIPK1) and the subsequent assembly of necrosome in a time-dependent manner, as well as suppressing NF-κB activation and decreasing TNF-α, IL-1ß, IL-6 and IL-8 expression. Silencing of AHR aggravated necroptosis and inflammation of NCM460 cells, and did not be ameliorated by I3C. Furthermore, AHR activation induces the expression of inhibitor of apoptosis proteins (IAPs) and the ubiquitination of RIPK1. In conclusion, I3C exerts a protective effect in DSS-induced colitis mice models by alleviating the necroptosis and inflammation of IECs through activating AHR.
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Colite Ulcerativa/metabolismo , Células Epiteliais/metabolismo , Inflamação/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Colite Ulcerativa/tratamento farmacológico , Células Epiteliais/efeitos dos fármacos , Inflamação/tratamento farmacológico , Intestinos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
Cinnarizine is a weak base, which can produce supersaturation and precipitation during gastrointestinal transit, affecting its absorption in vivo. Therefore, it is necessary to investigate whether the oral bioavailability of cinnarizine can be improved after co-administration with precipitation inhibitors or not. In order to evaluate the pharmacokinetic behavior of cinnarizine in rats, a simple, rapid, sensitive, and environmentally friendly supercritical fluid chromatography-tandem mass spectrometric method was established and validated. In this method, flunarizine, a structural analogue of cinnarizine, was selected as the internal standard, and cinnarizine was extracted from rat plasma using evaporation-free liquid-liquid extraction method. The analytes were separated on a Torus 1-AA column (3.0 mm × 100 mm, 1.7 µm) within 2.0 min, using a gradient elution procedure. The transitions of cinnarizine and flunarizine were m/z 369.1 â 167.1 and m/z 405.1 â 203.1, respectively. Cinnarizine showed good linear correlation in the range of 1-500 ng/ml with a lower limit of quantification of 1 ng/ml. The intra- and interday precision and accuracy of all quality control samples were within ±15%. This high-throughput, accurate, sensitive, and reproducible method has been successfully applied to study the effects of the precipitation inhibitor cinnarizine on the pharmacokinetics in rats.
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Cromatografia com Fluido Supercrítico , Cinarizina , Animais , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia com Fluido Supercrítico/métodos , Extração Líquido-Líquido , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodosRESUMO
Recent studies strongly suggest that atorvastatin combination therapy with tangeretin could be beneficial in the treatment of hyperlipidemia. This study aimed to investigate the pharmacokinetic interactions among atorvastatin, its active metabolite 2-hydroxy atorvastatin, and tangeretin after oral administration of atorvastatin with tangeretin in rats. A rapid, selective, and sensitive assay was developed and validated based on ultra-high performance supercritical fluid chromatography-tandem mass spectrometry for the simultaneous measurement of atorvastatin, 2-hydroxy atorvastatin, and tangeretin concentrations in rat plasma. Chromatographic separation of the analytes was conducted on an ACQUITY Torus 1-AA column in gradient elution mode. The mass transition ion pairs were m/z 559.0â440.0 for atorvastatin, m/z 575.2â440.0 for 2-hydroxy atorvastatin, m/z 373.0â358.1 for tangeretin, and m/z 254.8â136.7 for daidzein (internal standard). Calibration curves showed good linear correlations at the following concentration range: 1-400 (r = 0.9952), 1-400 (r = 0.9980), and 3-1200 (r = 0.9945) for atorvastatin, 2-hydroxy atorvastatin, and tangeretin, respectively. The method was fully validated and satisfied the acceptance criteria recommended by the United States Food and Drug Administration. Finally, it was successfully applied in a pharmacokinetic study in rats to evaluate the pharmacokinetic behavior of atorvastatin, 2-hydroxy atorvastatin, and tangeretin.
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Cromatografia com Fluido Supercrítico , Espectrometria de Massas em Tandem , Ratos , Animais , Espectrometria de Massas em Tandem/métodos , Atorvastatina , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Renal colic is a surgical emergency in pregnancy that is caused by a range of non-obstetric factors and known to occur more frequently during the second and third trimesters. Several studies have reported that up to 70-80% of stones pass spontaneously during pregnancy. There are some patients will not pass their stones and will ultimately require surgical intervention. Through retrospective analysis of the clinical data of 212 pregnant women with renal colic, the predictive factors of pregnant women with renal colic in need of surgical intervention were determined. METHODS: We conducted a retrospective review of 212 pregnant women presenting with renal colic between 1st January 2009 and 31st December 2020. Univariate and multivariate analyses identified a range of predictive variables for surgical intervention. In addition, we used receiver operating characteristic curve analysis to evaluate the predictive power of our model and created a nomogram for clinical application. RESULTS: Of the 212 patients presenting with acute renal colic in pregnancy, 100 patients (47.2%) underwent surgical intervention and 112 patients (52.8%) were treated conservatively. Univariate analysis identified significant differences between the two groups with regards to fever, the duration of pain, white blood cells, C-reactive protein, ureteral stone size, hydronephrosis, and stone location. Multivariate analysis further identified a number of independent predictors for surgical intervention, including fever, a duration of pain ≥ 4 days, a ureteral stone size ≥ 8 mm, and moderate or severe hydronephrosis. CONCLUSIONS: We identified several independent predictors for surgical intervention for renal colic in pregnancy. Fever, a duration of pain ≥ 4 days, a ureteral stone size ≥ 8 mm, and moderate/severe hydronephrosis, play significant roles in predicting surgical intervention. Our nomogram can help to calculate the probability of surgical intervention in a simple and efficient manner. Prospective studies are now required to validate our model.
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Complicações na Gravidez/cirurgia , Cólica Renal/cirurgia , Adulto , Feminino , Humanos , Gravidez , Complicações na Gravidez/etiologia , Cólica Renal/etiologia , Estudos RetrospectivosRESUMO
This review evaluates the ability of the fibrosis index based on four factors (FIB-4) identifying fibrosis stages, long-time prognosis in chronic liver disease, and short-time outcomes in acute liver injury. FIB-4 was accurate in predicting the absence or presence of advanced fibrosis with cut-offs of 1.0 and 2.65 for viral hepatitis B, 1.45 and 3.25 for viral hepatitis C, 1.30 (<65 years), 2.0 (≥65 years), and 2.67 for non-alcoholic fatty liver disease (NAFLD), respectively, but had a low-to-moderate accuracy in alcoholic liver disease (ALD) and autoimmune hepatitis. It performed better in excluding fibrosis, so we built an algorithm for identifying advanced fibrosis by combined methods and giving work-up and follow-up suggestions. High FIB-4 in viral hepatitis, NAFLD, and ALD was associated with significantly high hepatocellular carcinoma incidence and mortality. Additionally, FIB-4 showed the ability to predict high-risk varices with cut-offs of 2.87 and 3.91 in cirrhosis patients and predict long-term survival in hepatocellular carcinoma patients after hepatectomy. In acute liver injury caused by COVID-19, FIB-4 had a predictive value for mechanical ventilation and 30-day mortality. Finally, FIB-4 may act as a screening tool in the secondary prevention of NAFLD in the high-risk population.
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COVID-19 , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Fibrose , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
We developed an electrochemical trifluoromethylation of thiophenols without the use of metal catalysts and oxidants. This reaction features mild reaction conditions, readily available substrate, as well as moderate to good yields. In addition, this protocol can be easily scaled up with moderate efficiency.
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Hidrocarbonetos Fluorados , Mesilatos , Fenóis , Compostos de SulfidrilaRESUMO
A valine carbamate prodrug of naringenin (NAR) called 4'V was synthesized to enhance its oral bioavailability because of low water solubility and poor membrane permeability of NAR. This study developed and fully validated a sensitive, rapid, and robust HPLC-MS/MS method for the simultaneous determination of NAR and 4'V in plasma. The analytes were treated using liquid-liquid extraction, separated on a Phenomenex Kinetex XB-C18 column, and detected using a triple-quadrupole tandem mass spectrometer equipped with an electrospray ionization interface. The analytes were eluted within only 4 min by gradient procedure. The excellent linear correlations were validated over the range of 4-400 ng/mL (r = 0.9990) for NAR and 2-2000 ng/mL (r = 0.9951) for 4'V, with lower limits of quantification of 4 and 2 ng/mL, respectively. For all quality control samples, the intra-day and inter-day precision and accuracy were within ±15%. The validated method was economical, high throughput, and reliable and was first successfully applied to a pharmacokinetic study of NAR and 4'V after oral administration to Sprague-Dawley rats. The results of the pharmacokinetic study demonstrated that the idea of amino acid carbamate prodrug is a promising strategy to improve the bioavailability of NAR.
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Carbamatos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Flavanonas/sangue , Espectrometria de Massas em Tandem/métodos , Valina/sangue , Animais , Disponibilidade Biológica , Carbamatos/química , Carbamatos/farmacocinética , Flavanonas/química , Flavanonas/farmacocinética , Modelos Lineares , Masculino , Pró-Fármacos , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Valina/química , Valina/farmacocinéticaRESUMO
OBJECTIVE: The study aimed to recognize potential molecular targets and signal pathways whereby phenolic environmental estrogen promotes the proliferation of uterine leiomyoma cells. METHODS: Primary cultured cell lines of uterine leiomyoma were treated with 0.1% DMSO, 10.0µmol/L Bisphenol A (BPA), and 32.0µmol/L Nonylphenol (NP) for 48 h before RNA-seq was performed. Those genes affected by BPA and NP were identified. Then, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and Protein-protein Interaction (PPI) analysis were performed. Quantitative real-time polymerase chain reaction (q-PCR) and western blot were used to verify the differentially expressed gene and protein. RESULTS: Compared to with the control group, 739 differentially expressed genes were identified in both the BPA group and the NP group. GO enrichment analysis showed that the most enriched GO terms were connective tissue development and G1/S transition of mitotic cell cycle, and extracellular matrix. The results of KEGG enrichment analysis showed that differentially expressed mRNA were enriched mainly in three primary pathways, including environmental information processing, human diseases, and cellular processes. The cell cycle, PI3K-Akt signaling pathway are significantly enriched. The q-PCR and western blot verified the cell cycle associated genes and proteins were upregulated in both BPA group and NP group. Both BPA and NP activated the PI3K-AKT signaling pathway. CONCLUSION: Phenolic environmental estrogens may promote the proliferation and cell cycle progression of uterine leiomyoma cells through rapid non-genomic ER signaling, which leads to disordered cell cycle regulation and accelerates the transition of the cell cycle from G0/G1 phase to S phase. In addition, as an external stimulant, phenolic estrogen promotes the upregulation of inflammatory factors in uterine leiomyomas.
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Poluentes Ambientais/toxicidade , Estrogênios/toxicidade , Fenóis/toxicidade , Transcriptoma/fisiologia , Compostos Benzidrílicos , Linhagem Celular Tumoral , Poluentes Ambientais/metabolismo , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Leiomioma/genética , Leiomioma/metabolismo , Fenóis/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismoRESUMO
Propolis has a very complex composition, with antibacterial, anti-inflammatory and other properties. To determine the composition of ethanol extracts of Brazilian green propolis (EEP-B) and their protective effect on mouse aortic endothelial cells (MAECs), the chemical composition of EEP-B was analysed by UPLC/Q-TOF-MS/MS, and the protective effect of EEP-B on the proliferation of lipopolysaccharide (LPS)-induced MAECs was determined by Cell Counting Kit-8 (CCK-8) assays. The protein levels of inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin- 6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA), and ICAM-1, VCAM-1 and MCP-1 expressions were analysed by western blotting. The results showed that a total of 24 compounds belonging to cinnamic acids and flavonoids, including 3,5-diisopentenyl-4-hydroxycinnamic acid (artepillin C), kaempferide, 3-isoprenyl p-coumaric acid, pinocembrin and 4'-methoxy pinobanksin, were identified in EEP-B. Among them, a new component, suggested to be 5-isoprenyl caffeic acid p-coumaric acid ester, was reported for the first time. The LPS-induced levels of TNF-α, IL-6, ICAM-1, VCAM-1 and MCP-1 were downregulated in response to 5, 10 and 20 µg/mL EEP-B. This study revealed that EEP-B could reduce LPS-induced inflammatory reactions, improve cell survival, and protect MAECs by regulating ICAM-1, VCAM-1 and MCP-1 expression. These findings could provide a theoretical basis for MAEC treatment using EEP-B.
Assuntos
Anti-Inflamatórios/química , Células Endoteliais/metabolismo , Própole/química , Animais , Anti-Inflamatórios/farmacologia , Quimiocina CCL2/metabolismo , Células Endoteliais/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
Hepatitis B constitutes a severe public health challenge in China. The Community-based Collaborative Innovation hepatitis B (CCI-HBV) project is a national epidemiological study of hepatitis B and has been conducting a comprehensive intervention in southern Zhejiang since 2009.The comprehensive intervention in CCI-HBV areas includes the dynamic hepatitis B screening in local residents, the normalised treatment for hepatitis B infections and the upcoming full-aged hepatitis B vaccination. After two rounds of screening (each round taking for 4 years), the initial epidemiological baseline of hepatitis B in Qinggang was obtained, a coastal community in east China. By combining key data and system dynamics modelling, the regional hepatitis B epidemic in 20 years was predicted.There were 1041 HBsAg positive cases out of 12 228 people in Round 1 indicating HBV prevalence of 8.5%. Of the 13 146 people tested in Round 2, 1171 people were HBsAg positive, with a prevalence of 8.9%. By comparing the two rounds of screening, the HBV incidence rate of 0.192 per 100 person-years was observed. By consulting electronic medical records, the HBV onset rate of 0.533 per 100 person-years was obtained. We generated a simulated model to replicate the real-world situation for the next two decades. To evaluate the effect of interventions on regional HBV prevalence, three comparative experiments were conducted.In this study, the regional hepatitis B epidemic in 20 years was predicted and compared with HBV prevalence under different interventions. Owing to the existing challenges in research methodology, this study combined HBV field research and simulation to provide a system dynamics model with close-to-real key data to improve prediction accuracy. The simulation also provided a prompt guidance for the field implementation.