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Resumen Introducción: La mortalidad por intoxicaciones agudas de sustancias psicoactivas representa un problema de salud pública, especialmente en personas jóvenes. El objetivo del estudio fue crear un perfil de las víctimas mortales por intoxicación aguda en Costa Rica entre los años 2012 y 2021 asociado al consumo de sustancias psicoactivas y drogas de abuso. Materiales y métodos: Se recopilaron datos de Sección de Patología Forense del Departamento de Medicina Legal en Costa Rica, con los cuales se realizó una revisión de las víctimas mortales por intoxicaciones agudas a partir del 1 de enero de 2012 hasta el 31 de diciembre de 2021. La revisión incluyó las siguientes variables: variables epidemiológicas: sexo, edad, nacionalidad, ocupación, estado civil, provincia, consumo frecuente asociado, manera de muerte, tipo de sustancia y lugar de intoxicación. Resultados: De los 456 casos de muertes asociados a intoxicaciones agudas por etanol, metanol, benzodiacepinas, anfetaminas, heroína, cocaína y mixtas; reportados entre el 1 de enero de 2012 y el 31 de diciembre de 2021: el año que más casos reportó fue 2020; 82% de las víctimas fueron hombres y 18% mujeres; las principales edades de las personas reportadas abarcan entre 41 y 60 años. 80% de las personas eran costarricenses; San José fue la provincia con mayor número de casos de intoxicación letal, siendo el domicilio el sitio más frecuente. 14% de las víctimas eran desempleadas; 77% de las personas presentaban algún trastorno de la adicción o consumo frecuente de alguna de las sustancias estudiadas. La mayoría de muertes fueron de manera accidental. Conclusiones: El perfil predominante de las víctimas fue: masculino, entre 41 y 60 años, costarricense, de estado civil indeterminado o soltero, desempleado, que muere de manera accidental, en su domicilio, por intoxicación aguda con alcohol o mixta (alcohol y cocaína).
Abstract Introduction. Mortality from acute poisoning of psychoactive substances represents a public health problem, especially in young adults. The purpose of the study was to create a profile of fatalities due to acute poisoning in Costa Rica between 2012 and 2021 associated with the consumption of psychoactive substances and drugs of abuse. Materials and methods. Data were collected from the Forensic Pathology Section of the Legal Medicine Department in Costa Rica, then a review of fatalities due to acute poisoning was carried out from January 1, 2012 to December 31, 2021. The review included the following epidemiological variables: sex, age, nationality, occupation, marital status, province, consumption associated, manner of death, type of substance, and place of intoxication. Results. Out of the 456 reported cases of deaths associated with acute intoxication with ethanol, methanol, benzodiazepines, amphetamines, heroin, cocaine, and mixed substances between January 1, 2012, and December 31, 2021: the year with the highest number of cases reported was 2020; 82% of the victims were male, and 18% were female; the main age group of reported victims ranged from 41 to 60 years old. 80% of the victims were Costa Rican, and San Jose was the province with the highest number of lethal intoxication cases, with the home being the most frequent site. 14% of the victims were unemployed, and 77% of the individuals had some addiction disorder or frequent consumption of one of the studied substances. The majority of deaths were accidental. Conclusion. The main profile of the victims was male, between 41 and 60 years old, Costa Rican, of indeterminate or single marital status, unemployed, who died accidentally, at home, due to acute intoxication with alcohol or a mixture of substances (alcohol and cocaine).
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OBJETIVO: Verificar qual o tratamento mais indicado para a prevenção e redução dos sinais e sintomas de abstinência em crianças criticamente doentes por meio de uma revisão sistemática da literatura mundial. MÉTODO: A revisão sistemática será conduzida conforme a metodologia PRISMA e Cochrane, com registro no PROSPERO, sob o número de ID CRD42021274670, nas respectivas bases de dados PubMed, LILACS, Embase, Web of Science, Cochrane, CINAHL, Cochrane Database Systematic Review e CENTRAL. As buscas serão realizadas por dois avaliadores independentes, um terceiro realizará o intermédio se necessário. Os dados serão inseridos no programa de software Zotero que irá excluir os artigos duplicados, após o material selecionado será transferido para planilha Excel em instrumento próprio. Os estudos serão classificados quanto ao seu nível de evidência, viés e fator de risco. Os resultados serão analisados e tabulados e discutidos a fim de melhor compreensão dos resultados. Se possível, serão realizadas meta-análises para os resultados agregados.
OBEJECTIVE: To verify the most appropriate treatment for the prevention and reduction of the signs and symptoms of abstinence in critically ill children through a systematic review of the world literature. METHOD: The systematic review will be conducted according to the PRISMA and Cochrane methodology, with registration at PROSPERO, under the ID number CRD42021274670, in the respective databases, PUBMed, LILACS, Embase, Web of Science, Cochrane, CINAHL, Cochrane Database Systematic Review, and CENTRAL, searches will be carried out by two independent evaluators, and a third party will perform the intermediate if necessary. The data will be entered into the Zotero software program that will delete duplicate articles after the selected material is transferred to an Excel spreadsheet on its instrument. The studies will be classified according to their level of evidence, bias, and risk factors. The results will be analyzed, tabulated, and discussed to understand the results better. If possible, meta-analyzes will be carried out for the aggregated results.
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Humanos , Criança , Síndrome de Abstinência a Substâncias , Unidades de Terapia Intensiva Pediátrica , Saúde da Criança , Estado Terminal , Revisões Sistemáticas como Assunto , AnalgesiaRESUMO
Background Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants that possess potential toxicity to the human body. The production and utilization of diverse emerging PFAS have resulted in widespread human exposure. Therefore, it is imperative to establish a quantitative methodology encompassing a wide range of PFAS for a comprehensive assessment of human exposure to these compounds. Objective To establish a high-throughput quantitative method for the simultaneous determination of 53 PFAS in human serum based on ultra-high-performance liquid chromatography-Q Exactive high resolution mass spectrometry (UPLC-Q Exactive HRMS). Methods The extraction recoveries of hydrophilic-lipophilic balance (HLB) column, weak anionexchange (WAX) column, and 96-well WAX μElution plate were compared to select the SPE column with the highest recovery. The retention time and peak shape of the target compounds were compared between ACQUITY UPLC BEH C18 column and Accucore aQ column, and the more cost-effective column was chosen. The effects of adding different levels of ammonium formate (0, 2, 5 and 10 mmol·L−1) in mobile phase on peak shape and target response were compared to determine the optimal buffer salt concentration. The optimal spray voltage was obtained by comparing −2 kV and −4 kV. The proposed method was validated from the aspects of selectivity, standard curve, limits of detection, precision, accuracy, and matrix effect. The method was applied to 142 umbilical serum samples. Results The best recovery rate (64%-118%) was achieved by using 96-well WAX μElution plate. The optimal separation and peak shape were obtained by utilizing Accucore aQ column with H2O-methanol (containing 5 mmol·L−1 ammonium formate) as the mobile phase. Less in-source collision and better target response were observed when the spray voltage was set to −2 kV. All target analytes had a good linearity, with R2 > 0.99. The limits of detection ranged from 0.01 to 0.50 μg·L−1, and the recovery ranged from 69% to 127% with the precision less than 26%. A total of 31 PFAS were detected in the 142 actual samples, among which 14 PFAS had a detection frequency over 50%. Perfluorooctanoic acid showed the highest median concentration of 4.16 μg·L−1, followed by 6:2 chlorinated polyfluorinated ether sulfonate and perfluorooctane sulfonates (3.50 μg·L−1 and 1.59 μg·L−1, respectively). Conclusion In this study, we establish a UPLC-Q Excative HRMS method for simutanious determination of 53 PFAS concentrations in serum. This method has the advantages of wide coverage of PFAS, good selectivity, and easy operation, and is suitable for biological detection with a large sample size.
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Idiopathic oligoasthenospermia （IO） has been increasingly emphasized in the diagnosis and treatment of male infertility. Oxidative stress damage directly affects sperm quality and spermatogenesis， constituting a major causative factor of IO. Firstly， due to its high content of polyunsaturated fatty acids， the sperm plasma membrane is highly sensitive to reactive oxygen species （ROS）， leading to lipid peroxidation accumulation and even inducing ferroptosis. Secondly， deficient downstream key proteins in the base excision repair pathway render sperm unable to repair extensive DNA oxidative damage under oxidative stress. Simultaneously， under oxidative stress， the apoptotic pathway of sperm is cascade-activated， causing rapid loss of motility. ROS further disrupts the hypothalamic-pituitary-gonadal axis， inhibiting testosterone production and ultimately affecting spermatogenesis. Wuzi Yanzongwan，in line with traditional Chinese medicine theory of treating IO through "nourishing kidney essence and harmonizing Yin and Yang"， clinically demonstrates its ability to improve sperm morphology， count， and motility， thereby enhancing male fertility. The research on the pharmacological constituents of Wuzi Yanzongwan primarily involves establishing a characteristic spectrum of Chinese medicine to achieve quality control and exploring the pharmacology of effective components. Studies have found that its main active ingredients consist of flavonoids and phenylpropanoids. Specifically， compounds such as hyperin， acteoside， kaempferol， and schisandrin A are identified as the primary active substances and quality control components. These compounds exhibit strong antioxidant activity and have been partly applied in research related to reproductive endocrine disorders. Tripterygium glycoside is primarily used for modeling of oxidative stress-induced IO. It leads to the accumulation of various lipid peroxides in testicular tissues and concurrently compromises the body's antioxidant capacity. Mechanistic studies have found that Wuzi Yanzongwan can inhibit elevated ROS levels in IO models and enhance the body's antioxidant capacity， thereby ameliorating inflammation， suppressing cell apoptosis， promoting testosterone production， and ultimately alleviating the decline in sperm quality and spermatogenesis caused by oxidative stress.
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A new method for simultaneous determination of 23 kinds of per-and polyfluoroalkyl substances(PFASs)(13 kinds of perfluoro carboxylic acids,4 kinds of perfluoro sulfonic acids,and 6 kinds of new substitutes)in plant leaf tissue by ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)using automatic online solid phase extraction(SPE)to remove the matrix interference components in plant crude extracts was developed.The plant leaf samples were extracted twice with 1%formic acid-methanol solution,then evaporated to dry,redissolved with 70%methanol solution,and directly injected for analysis.After 23 kinds of target PFASs were purified automatically by online SPE with a WAX column,the six-way valve was switched to rinse PFASs onto an alkaline mobile phase system-compatible C18 analytical column.Then,the 23 kinds of target PFASs were separated within 16 min by gradient elution using a binary mobile phase system of methanol/water(Containing 0.4%ammonium hydroxide).Tandem mass spectrometry was performed in multiple reaction monitoring(MRM)mode for online detection of various PFASs,and quantification was carried out by internal standard method.The results of the method validation showed that satisfactory average recoveries of 23 kinds of PFASs in plant leaf samples(64.2%-125.5%),precision(relative standard deviations(RSDs)of 0.7%-12.8%),linearity(R2＞0.990),and sensitivity(the detection limits(S/N=3)were in the range of 0.02-0.50 μg/kg)were achieved.Finally,this method was used to detect PFASs in the marine green tide algae(Enteromorpha prolifera)and several tree leaves,and a total of 6 kinds of PFASs were detected,in which PFBA was the main contaminant.Compared with the reported offline SPE methods,the proposed online SPE technique significantly simplified the sample pretreatment process and provided an automatic,simple,and environment-friendly method for the routine monitoring of legacy and emerging PFASs in plant tissues.
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Gut microbiome plays an important role in maintaining lifelong health. Infancy is a critical period for the establishment of gut microbiota, which is influenced by many factors, including delivery methods, antibiotics, and feeding mode. Human milk contains a variety of bioactive factors, such as human milk oligosaccharide, secretory immunoglobulin, and human milk microbiota, which play important roles in the establishment and stability of newborn microbiota. This article presents the latest research progress on the effects of the aforementioned bioactive factors in breast milk on the colonization and development of infant microbiota, and explains how these substances affect immune function through intestinal bacteria.
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Background Per- and poly-fluoroalkyl substances (PFAS) are a class of emerging persistent organic pollutants, and their negative health impacts have been widely concerned. There is a lack of epidemiological studies on the associations of PFAS exposure with lipid homeostasis. Objective To investigate the associations of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) exposure with blood lipid levels and dyslipidemia in middle-aged and elderly women. Methods This study was based on 795 middle-aged and elderly women from a female sub-cohort of the Dongfeng-Tongji cohort study, excluding the participants without blood lipid measurements and/or reported use of lipid-lowering drugs at baseline. The concentrations of plasma PFOS and PFOA were measured by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The concentrations of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured using an automatic analyzer. The normally distributed continuous variables were presented as mean ± standard deviation (\begin{document}$ \bar{x}\pm s) $\end{document}, while the skewedly distributed continuous variables were presented as median (M) and the 25th and 75th percentiles (P25, P75). Generalized linear models (GLM), generalized additive models (GAM), and logistic regression models were applied to evaluate the associations of PFOS and PFOA exposure with blood lipid levels and the risk of dyslipidemia. Stratified analyses were also implemented to explore potential modification effects of sociodemographic characteristics, lifestyles, and menopause on associations of PFOS and PFOA exposure and blood lipids. Results The \begin{document}$ \bar{x}\pm s $\end{document} of baseline age for the study participants was (59.4±8.6) years old, and their baseline body mass index (BMI) was (24.3±3.4) kg·m−2. The M (P25, P75) of baseline plasma concentrations for PFOS and PFOA were 9.96 (6.24, 15.09) μg·L−1 and 1.20 (0.84, 1.80) μg·L−1 respectively. The GLM analysis showed that plasma concentration of PFOS was positively associated with serum HDL-C [b (95%CI): 0.04 (0.01, 0.07)]. The plasma concentration of PFOA was also positively associated with serum TC [b (95%CI): 0.05 (0.02, 0.08)] and serum LDL-C [b (95%CI): 0.05 (0.01, 0.09)]. No significant association was observed between plasma PFOS and serum TC, TG, or LDL-C, nor between plasma PFOA and serum TG or HDL-C. The stratified analyses showed that the association between PFOA and LDL-C was significant among the participants aged <60 years old [b (95%CI): 0.06 (0.01, 0.11), P=0.014]. A modification effect was observed for age on the association of plasma PFOA with serum LDL-C, with Pinteraction=0.046. The analysis of the associations between PFOS/PFOA exposure and the risk of dyslipidemia showed that an increased plasma PFOA was significantly associated with an increased risk of hypercholesterolemia, with an OR (95%CI) of 1.69 (1.23, 2.15). No association was observed between PFOS exposure and the risk of dyslipidemia. Conclusion This cross-sectional study reveals that common PFAS exposure could affect the homeostasis of blood lipids based on the female sub-cohort of the Dongfeng-Tongji cohort, which provides new evidence for the negative health impact of PFAS.
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Background Per- and polyfuoroalkyl substances (PFAS) are categorized as persistent organic pollutants and commonly detected in humans, and their toxicity has attracted widespread attention. However, few studies have reported comparison of PFAS levels and potential factors between women pregnant using assisted reproduction technology (ART) and women pregnant naturally. Objective To analyze and compare serum concentrations and sociodemographic determinants of PFAS in pregnant women conceiving through ART and conceiving naturally from Shanghai. Methods Based on the China National Birth Cohort (CNBC) in Shanghai from 2017 to 2019, 333 pregnant women conceiving through ART and 689 pregnant women conceiving naturally were recruited during the same period as study subjects. The concentrations of 32 PFAS were measured in early-pregnancy serum of all pregnant women, and four PFAS with the highest co-exposure levels in both groups were included in the subsequent analysis. Multiple linear regression models were performed to evaluate the associations of sociodemographic factors with serum PFAS concentrations in the two groups respectively. Beta coefficients and 95% confidence intervals (CI) were exponentiated to calculate the ratio of the geometric mean (GM) of PFAS concentrations after each unit change in the independent variable. Results Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), 6∶2 chlorinated polyfluoroethersulfonic acid (6∶2 Cl-PFESA), and perfluorohexanesulfonic acid (PFHxS) were four major PFAS in serum of pregnant women conceiving through ART and conceiving naturally, and the concentrations of PFOA, PFOS, and 6∶2 Cl-PFESA were higher in pregnant women conceiving through ART than in pregnant women conceiving naturally (P <0.05). The results of multiple linear regression analysis showed that age at pregnancy and household income were associated with serum PFAS levels in both groups. The serum concentrations of PFOS were higher in pregnant women aged ≥35 years old who conceiving through ART (GM ratio=1.26, 95%CI: 1.04, 1.54) and conceiving naturally (GM ratio=1.24, 95%CI: 1.08, 1.42) than pregnant women aged <30 years old respectively. Pregnant women conceiving through ART and conceiving naturally whose household annual income >300000 CNY had lower serum concentrations of PFOA [GM ratio (95%CI): 0.82 (0.72, 0.95) and 0.89 (0.81, 0.97), respectively] and PFHxS [GM ratio (95%CI): 0.66 (0.51, 0.86) and 0.77 (0.66, 0.90), respectively] than those women whose household annual income <200000 CNY. Additionally, pregnant women conceiving naturally with a graduate education or above had lower serum 6∶2 Cl-PFESA concentrations than women with an education below college (GM ratio: 0.81), and multiparous pregnant women conceiving naturally had higher serum concentrations of PFOS, 6∶2 Cl-PFESA, and PFHxS than primiparous pregnant women (GM ratio: 1.14, 1.25, and 1.27 respectively). Conclusion Although differences in serum PFAS levels are found between pregnant women conceiving through ART and women conceiving naturally in this study, maternal age and household income are common determinants of PFAS exposure levels in both populations. We find no special sociodemographic factors to affect PFAS concentrations of pregnant women conceiving through ART compared to pregnant women conceiving naturally. Further research is required to explore other potential factors.
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This study aimed to identify the related substances of phloroglucinol injection by two-dimensional liquid chromatography quadrupole time-of-flight mass spectrometry (2D-LC-Q-TOF/MS). The first-dimensional separation was carried out on an HSS T3 (250 mm × 4.6 mm, 5 μm) column by gradient elution using 1.36 g·L-1 potassium dihydrogen phosphate buffer solution (pH adjusted to 3.0 with diluted phosphoric acid) and acetonitrile as the mobile phases. The separated components were then trapped in switch valve tube lines respectively and delivered to the second-dimensional desalting gradient elution which was performed with a BDS C18 (100 mm × 4.6 mm, 2.4 μm) column using 0.1% formic acid and methanol as the mobile phases. After rapid desalting, electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry was used for determining the accurate masses and elemental compositions of the parents and their product ions for both phloroglucinol and its related substance. Structures of the related substances were then figured out by mass spectrometry elucidation, organic reaction mechanism analysis, and/or comparison with reference substances. Under the established analytical conditions, phloroglucinol and its related substances were adequately separated, 17 main related substances were detected and identified in the injection and its stressed samples for the first time. The identification results can provide reference for the quality control of phloroglucinol injection.
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The chloroplast genome encodes many key proteins involved in photosynthesis and other metabolic processes, and metabolites synthesized in chloroplasts are essential for normal plant growth and development. Root-UVB (ultraviolet radiation B)-sensitive (RUS) family proteins composed of highly conserved DUF647 domain belong to chloroplast proteins. They play an important role in the regulation of various life activities such as plant morphogenesis, material transport and energy metabolism. This article summarizes the recent advances of the RUS family proteins in the growth and development of plants such as embryonic development, photomorphological construction, VB6 homeostasis, auxin transport and anther development, with the aim to facilitate further study of its molecular regulation mechanism in plant growth and development.
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Feminino , Gravidez , Humanos , Raios Ultravioleta , Transporte Biológico , Cloroplastos/genética , Desenvolvimento Embrionário , Desenvolvimento Vegetal/genéticaRESUMO
Objective To determine the related substances in the pharmaceutical excipient triacetin by gas chromatography(GC).Methods Rtx-1701 and DB-1701 chromatographic column(30 m×0.25 mm,0.25 μm)was used,with nitrogen as the carrier gas,the flow rate was 1.5 mL/min,the inlet temperature was 200℃,the hydrogen flame ionization detector was used,the temperature of the measuring instrument was 250℃,and the program heating was used.Results Under this chromatographic condition,each substance could be effectively separated,and showed good linearity at 2-40 μg/mL(r>0.99).The recovery rates of acetic acid,glycerol,1-monoglyceryl acetate,1,2-diglyceryl acetate and 1,3-diglyceryl acetate were 100.7%(RSD=3.12%),95.1%(RSD=3.66%),99.43%(RSD=4.62%),103.66%(RSD=5.88%)and 103.15%(RSD=4.17%)(n=6),respectively.Conclusion This method has high accuracy and good reproducibility,which can be used for the determination of related substances in the triacetin,and provides a reference for the quality standard of triacetin.
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Objective@#To explore the effects of protein powder on the bioavailability of perfluoroalkyl substances (PFASs) in blood and kidneys of rats and renal function change.@*Methods@#Twenty-four rats of the SD strain were randomly divided into the negative control group, PFASs group and protein powder group, with 8 rats (half males and half females) in each group. PFASs included 13 perfluorocarboxylic acids (PFCAs) and 8 perfluorosulfonic acids (PFSAs), and the mixture was used as a test subject for intervention. The rats in the negative control group were given deionized water at doses of 20 mL/kg·bw, in the PFASs group were given 5 mL/kg·bw of PFASs mixtures and 15 mL/kg·bw of deionized water, and in the protein powder group were given 5 mL/kg·bw of PFASs mixtures and 15 mL/kg·bw of protein powder (0.258 g/mL). After intervention for 28 successive days, body weight and kidney mass were weighed, and the kidney volume index was calculated. Serum creatinine and blood urea nitrogen were detected by an automatic biochemical analyzer. The PFCAs, PFSAs and PFASs contents were quantified in blood and kidney using ultra-high performance liquid chromatography-electrospray tandem mass spectrometry, and the bioavailability was estimated.@*Results@#There was no significant differences in kidney mass, kidney volume index, serum creatinine and blood urea nitrogen among the negative control group, PFASs group and protein powder group (all P>0.05). The bioavailability of blood PFCAs, PFSAs and PFASs in the protein powder group was not significantly different from the PFASs group (all P>0.05). Compared with the PFASs group, the bioavailability of PFCAs, PFSAs and PFASs were significantly increased in kidneys of male rats in the protein powder group (all P<0.05), while were not significant different in those of female rats (all P>0.05).@*Conclusion@#Protein powder at the dose of this study can significantly improve the bioavailability of PFASs in kidneys of male rats, while there no obvious effects on the bioavailability of blood PFASs and renal function.
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Microorganisms can form biofilms, complex, heterogeneous, multicellular communities that adhere to surfaces. Biofilm formation on the surface of structures in water will accelerate structures’ corrosion, seriously affect their service efficiency and life, and significantly impact the growth of animals, plants, and human life. Hence, clarifying the mechanism of biofilm formation contributes to developing new strategies to control biofilm formation on surface and then reduce infections, biofouling, and contaminations. Biofilm-targeting strategies include the regulation of established biofilms or the modulation of single-cell attachment. In most studies, physicochemical mechanism is frequently applied to explain the initial bacterial adhesion phenomena but rarely to explain other stages of biofilm formation. This review presents a five-step comprehensive description of the physicochemical process from film formation to biofilm maturation: (1) period of film formation; (2) period of bacterial adhesion; (3) period of extracellular-polymeric-substances (EPSs) membrane formation; (4) period of regulating biofilm by quorum sensing (QS); (5) period of biofilm maturation. We first clarify how the film formed by compound molecules affects the surface’s physicochemical properties and initial adhesion, summarizing many factors that affect bacterial adhesion. We then review the types of EPSs and signal molecules secreted by bacteria after irreversible adhesion, as well as their role and QS mechanism in biofilm maturation. Finally, we discuss how bacteria or microcolonies separate from the mature biofilm by physicochemical action and summarize the morphology and adhesion characterization methods after the biofilm matures. This review redefines the role of physicochemical in the whole process of biofilm formation and provides a theoretical basis for the prevention, removal, and utilization of biofilm and other related research fields.
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【Objective】 To detect endogenous heparin substance in patients with epidemic haemorrhagic fever (EHF) using thromboelastography (TEG) combined with conventional coagulation indices(CCTs), explore the value of TEG combined with CCTs in detecting coagulation function abnormalities in such patients, aiming at providing guidance for clinical treatment. 【Methods】 APTT, TT, TEG plain cup R value and TEG heparinase cup R value were tested in 35 EHF patients of mild/moderate stage, severe stage and recovery stage. Intergroup differences were analysed using Friedman ANOVA. 【Results】 The mean R and heparin cup R values were 7.5 and 6.7 for mild cases of EHF, and TT, R and heparinase cup R values were 16.9, 6.2 and 6.1 for recovering cases, respectively.The normal cup R and heparinase cup R values for mild cases, as well as the TT, R and heparinase cup R values for recovering cases, were normally distributed, and the rest were non-normally distributed. Changes in APTT and TT in EHF patients at different stages were significantly different (P<0.05). The patients′ TEG R-values (coagulation reaction time) also showed statistically significant differences in mild-moderate, severe and recovery periods (P<0.05). Prolonged APTT, TT and R values in the severe phase compared to the mild-moderate phase indicated that the patient′s coagulation function continued to decrease. The difference of R-values minus the heparanase cup R-values in EHF patients was statistically significant in the mild-moderate, severe, and recovery phases (P<0.05). Residual accumulation of endogenous heparin-like substances was higher in the severe phase than in the mild-moderate and recovery phases. 【Conclusion】 Patients with EHF exhibit significant differences in the values of APTT, TT and R at different stages of the disease. The combined detection using TEG and CCTs indicates that the accumulation of endogenous heparin-like substances is one of the most important causes of coagulation disorders in patients with EHF. The combination of TEG and CCTs can detect the accumulation of endogenous heparin-like substances in patients with EHF, which can provide a laboratory basis for clinicians to adopt targeted therapeutic regimen.
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ObjectiveTo determine the pharmacodynamic substance basis of Epimedii Folium（EF） and Epimedii Wushanensis Folium（EWF） in promoting osteogenic differentiation， and to establish a method to analyze the material basis of Chinese materia medica based on the correlation between chemical fingerprint and cellular metabolomics. MethodThe chemical fingerprints of 15 batches of EF with 4 species and 3 batches of EWF were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS）， and partial least squares-discriminant analysis（PLS-DA） was used to analyze the peak areas of chemical fingerprints of samples. The effects of different samples on proliferative activity of MC3T3-E1 osteoblast precursors， as well as the activity of alkaline phosphatase（ALP） in osteoblasts were detected by cell counting kit-8（CCK-8） and enzyme-linked immunosorbent assay（ELISA）. At the same time， UPLC-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to analyze the effects of different samples on the metabolomics of MC3T3-E1 cells， then metabolic peak table of osteogenic differentiation cells was constructed， and pharmacodynamic index mean Y0 was introduced into the peak table. PLS was used to calculate mean Y0 of each group， and the mean Y0 was added to the peak table of chemical fingerprint to construct the correlation between chemical fingerprint and cell metabolome， the pharmacodynamic components of EF and EWF that promote bone differentiation were screened according to variable importance in the projection（VIP） value>1. The pharmacodynamic effects of EF and EWF were evaluated according to the mean Y0 of each group. ResultThe chemical fingerprints of EF with different origins and EWF were completely separated. Compared with the blank group， the activity of MC3T3-E1 cells in EF and EWF groups was significantly increased， the activity of ALP in the Epimedium brevicornu（Gansu province）， E. koreanum and E. pubescens groups was significantly increased（P<0.05）. The results of cell metabolomics showed that the blank group and the model group had an obvious trend of separation. EF with different origins and EWF had different distance from the model group， indicating that EF with different origins and EWF had different effect on promoting osteogenic differentiation. Chemical fingerprint-cell metabolomics integration analysis screened 9 components closely related to the efficacy of EF and EWF， including diphylloside B， epimedin C， icariin， baohuoside Ⅰ， yinyanghuo B， β-anhydroicaritin， magnoflorine， cryptochlorogenic acid and quercetin. E. koreanum had the strongest effect on promoting osteogenic differentiation. ConclusionThis study determined that the material basis of EF and EWF promoting osteogenic differentiation were mostly flavonoids， alkaloids and organic acids， which provided ideas and methods for the screening of pharmacodynamic components and the prediction of therapeutic effect of Chinese materia medica.
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The study of biologically active substances-secondary metabolites of plants that exhibit geroprotective properties is an actual and popular direction in medicine to prevent early aging. This work aims to select the cultivation parameters for obtaining in vitro cell cultures of meadowsweet containing the largest amount of biologically active substances (BAS) for their further extraction as candidate substances for geroprotectors. To specify the effectiveness of the selected cell culture cultivation parameters, biomass growth for callus and root cultures, growth index, specific growth rate, and viability for suspension cultures was carried out. The study results made it possible to select the nutrient media for the cultivation of cell cultures of meadowsweet. It has been found that the greater the antioxidant activity of the extracts, the greater the antimicrobial properties it exhibits. In this study, cell cultures in vitro and alcohol extracts from the plant Filipendula ulmaria were considered as raw materials rich in candidate substances for geroprotectors. According to the data obtained, the plant is rich in hydroxybenzoic and salicylic acids, spireoside, avicularin, and hyperoside.
O estudo de substâncias biologicamente ativas - metabólitos secundários de plantas que apresentam propriedades geroprotetoras - é uma tendência atual e popular no campo da medicina para a prevenção do envelhecimento precoce. O objetivo deste trabalho foi selecionar os parâmetros de cultivo para obtenção de culturas celulares in vitro de Ulmária contendo a maior quantidade de substâncias biologicamente ativas (SBA), para sua posterior extração como substâncias candidatas a serem geroprotetoras. Para especificar a eficácia dos parâmetros selecionados de cultivo em cultura de células, foi realizada a análise de crescimento de biomassa para culturas de calos e raízes, índice de crescimento, taxa de crescimento específica e viabilidade para culturas em suspensão. Os resultados do estudo possibilitaram a seleção do meio nutriente para o cultivo de células de Ulmária. Verificou-se que, quanto maior a atividade antioxidante dos extratos, maiores eram as propriedades antimicrobianas exibidas. Neste estudo, culturas celulares in vitro e extratos alcoólicos da planta Filipendula ulmaria foram considerados matérias-primas ricas em substâncias candidatas a serem geroprotetoras. De acordo com os dados obtidos, a planta é rica em ácidos hidroxibenzoico e salicílico, espirosídeo, avicularina e hiperosídeo.
Assuntos
Plantas Medicinais/genética , Envelhecimento , Senilidade Prematura , AntioxidantesRESUMO
ABSTRACT BACKGROUND: Medical students demonstrate higher rates of substance use than other university students and the general population. The challenges imposed by the coronavirus disease 2019 (COVID-19) pandemic raised significant concerns about mental health and substance use. OBJECTIVES: Assess the current prevalence of substance use among medical students at the University of São Paulo and evaluate the impact of the COVID-19 pandemic on drug consumption. DESIGN AND SETTING: A cross-sectional study was conducted on 275 medical students from the University of São Paulo Medical School (São Paulo, Brazil) in August 2020. METHODS: Substance use (lifetime, previous 12 months, and frequency of use before and during the COVID-19 pandemic) and socioeconomic data were assessed using an online self-administered questionnaire. Symptoms of depression were assessed using the Patient Health Questionnaire-9. RESULTS: Alcohol was the most consumed substance in their lifetime (95.6%), followed by illicit drugs (61.1%), marijuana (60%), and tobacco (57.5%). The most commonly consumed substances in the previous year were alcohol (82.9%), illicit drugs (44.7%), marijuana (42.5%), and tobacco (36%). Students in the first two academic years consumed fewer substances than those from higher years. There was a decreasing trend in the prevalence of most substances used after the COVID-19 pandemic among sporadic users. However, frequent users maintained their drug use patterns. CONCLUSION: The prevalence of substance use was high in this population and increased from the basic to the clinical cycle. The COVID-19 pandemic may have affected the frequency of drug use and prevalence estimates.
RESUMO
Abstract The study of biologically active substances-secondary metabolites of plants that exhibit geroprotective properties is an actual and popular direction in medicine to prevent early aging. This work aims to select the cultivation parameters for obtaining in vitro cell cultures of meadowsweet containing the largest amount of biologically active substances (BAS) for their further extraction as candidate substances for geroprotectors. To specify the effectiveness of the selected cell culture cultivation parameters, biomass growth for callus and root cultures, growth index, specific growth rate, and viability for suspension cultures was carried out. The study results made it possible to select the nutrient media for the cultivation of cell cultures of meadowsweet. It has been found that the greater the antioxidant activity of the extracts, the greater the antimicrobial properties it exhibits. In this study, cell cultures in vitro and alcohol extracts from the plant Filipendula ulmaria were considered as raw materials rich in candidate substances for geroprotectors. According to the data obtained, the plant is rich in hydroxybenzoic and salicylic acids, spireoside, avicularin, and hyperoside.
Resumo O estudo de substâncias biologicamente ativas metabólitos secundários de plantas que apresentam propriedades geroprotetoras é uma tendência atual e popular no campo da medicina para a prevenção do envelhecimento precoce. O objetivo deste trabalho foi selecionar os parâmetros de cultivo para obtenção de culturas celulares in vitro de Ulmária contendo a maior quantidade de substâncias biologicamente ativas (SBA), para sua posterior extração como substâncias candidatas a serem geroprotetoras. Para especificar a eficácia dos parâmetros selecionados de cultivo em cultura de células, foi realizada a análise de crescimento de biomassa para culturas de calos e raízes, índice de crescimento, taxa de crescimento específica e viabilidade para culturas em suspensão. Os resultados do estudo possibilitaram a seleção do meio nutriente para o cultivo de células de Ulmária. Verificou-se que, quanto maior a atividade antioxidante dos extratos, maiores eram as propriedades antimicrobianas exibidas. Neste estudo, culturas celulares in vitro e extratos alcoólicos da planta Filipendula ulmaria foram considerados matérias-primas ricas em substâncias candidatas a serem geroprotetoras. De acordo com os dados obtidos, a planta é rica em ácidos hidroxibenzoico e salicílico, espirosídeo, avicularina e hiperosídeo.
RESUMO
No início dos anos 2000, as Novas Substâncias Psicoativas (NPS) emergiram de forma sem precedentes causando uma drástica mudança no mercado de drogas sintéticas mundial. Estas substâncias são sintetizadas para fins ilícitos e mimetizam o efeito psicoativo das drogas tradicionais. Até o momento, mais de 1000 substâncias foram reportadas mundialmente, representando um grande problema de saúde pública principalmente associado ao desconhecimento das suas propriedades toxicológicas. Por este motivo, métodos analíticos para detectar e quantificar estas substâncias em materiais biológicos são importantes nos casos de toxicologia analítica e forense. Contudo, a tendência de reduzir o impacto ambiental destas metodologias tem ganhado popularidade com a Toxicologia Analítica Verde (GAT). Portanto, o objetivo do presente trabalho foi desenvolver novas técnicas analíticas para analisar as principais classes de NPS em amostras biológicas enquanto aplicando os princípios sustentáveis estabelecidos pela GAT. Os resultados obtidos no presente trabalho são apresentados como coletânea de artigos científicos publicados em revistas. Estes estão descritos nos capítulos 4 a 8. No capítulo 4, uma revisão sobre os desafios no desenvolvimento de técnicas de preparo de amostra para fins forenses é abordada com foco no uso das matrizes secas. No Capítulo 5, está descrito a aplicação da microextração líquido-líquido dispersiva para catinonas sintéticas em amostras de sangue total e urina. No capítulo 6, o artigo descreve o desenvolvimento da técnica microextração líquido-líquido homogênea com solventes de hidrofilicidade comutável para canabinoides sintéticos em amostras de plasma. No capítulo 7, a microextração em fase líquida em placas de 96 poços, cunhada extração paralela em membranas artificiais líquidas, foi desenvolvida para diferentes classes de drogas de abuso, incluindo NPS. O capítulo 8 mostra o desenvolvimento de uma extração por eletromembrana também no formato de placa de 96 poços para catinonas sintéticas em amostras de sangue total. Em todos os trabalhos, as técnicas de extração foram desenvolvidas, otimizadas e validadas. Os princípios da GAT foram aplicados de diferentes formas, como reduzindo o volume de amostra, simplificando os procedimentos, evitando o uso de solventes orgânicos, dentre outros. Assim, alternativas mais sustentáveis para a análise de drogas de abuso em amostras biológicas foram apresentadas e estas ajudam a consolidar e difundir o conceito do desenvolvimento de métodos analíticos com consciência ambiental além de fornecer ferramentas para auxiliar o controle das NPS no país
In the early 2000s, New Psychoactive Substances (NPS) emerged and unprecedentedly changed the illicit drug market. These substances are synthesized for illicit purposes and mimic the psychoactive effect of traditional drugs of abuse. To date, more than 1000 substances have been reported worldwide, representing a major public health problem mainly associated with their mostly unknown toxicological properties. In this context, analytical methods able to detect and quantitate these new drugs in biological specimens are important in cases of analytical and forensic toxicology. However, reducing the environmental impact of these methodologies has recently gained popularity with Green Analytical Toxicology (GAT). Therefore, the aim of this work was to develop new analytical techniques to analyze the main classes of NPS in biological samples while applying the environmentally friendly principles established by GAT. The results obtained throughout the development of the present work were split into four papers (chapters 4-8). In chapter 4, a review of common challenges faced during the development of new sample preparation techniques for forensic applications is described focusing on the use of dried matrices. In chapter 5, the application of dispersive liquid-liquid microextraction for synthetic cathinones in whole blood and urine samples is described. In chapter 6, the application of the somewhat recent switchable hydrophilicity solvent-based homogenous liquidliquid microextraction to synthetic cannabinoids in plasma samples is reported. In chapter 7, liquid-phase microextraction in the 96-well plate format, termed parallel artificial liquid membrane extraction, for different classes of drugs of abuse, including NPS, in plasma samples is presented. In chapter 8, an electromembrane extraction in the 96-well plate format for synthetic cathinones in whole blood samples was developed. In this work, sample preparation techniques were developed, optimized and validated. The principles of sustainable chemistry in method development were applied in different ways, such as reducing the sample volume, simplifying procedures, avoiding the use of organic solvents, among others. Thus, greener alternatives were presented for the analysis of drugs of abuse in biological samples and contribute to consolidate and spread this trend of environmental consciousness during method development. Additionally, valuable techniques that can be used in the combat against NPS were provided
Assuntos
Psicotrópicos/efeitos adversos , Drogas Ilícitas/efeitos adversos , Toxicologia Forense/métodos , Espectrometria de Massa com Cromatografia Líquida/métodos , Canabinoides/farmacologia , Preparações Farmacêuticas/análise , Catinona Sintética/farmacologiaRESUMO
En la actualidad, la alogenosis iatrogénica es una condición reconocida en todo el orbe, especialmente en Latinoamérica, donde es evidente la ausencia de control en la administración de sustancias no reguladas con fines estéticos, lo que ha devenido un problema emergente por la magnitud de las complicaciones, ya que algunos productos, como aceites minerales, hidrocarburos, silicona industrial, generan graves consecuencias, tanto locales como sistémicas, en el organismo. Muchos países aún no han regulado la prohibición de esta práctica, aunque cada día son más las campañas para prevenirla; sin embargo, al mismo tiempo aumenta la incidencia de la enfermedad en todo el mundo por el incremento de estos procedimientos estéticos. Al respecto, en Cuba, el creciente número de afectados por esta causa evidencia vulnerabilidad en el cumplimiento de lo establecido hasta la fecha, por lo que se impone instaurar un marco legal de estricto cumplimiento que regule la inyección de sustancias modelantes con fines estéticos.
Currently, iatrogenic allogenosis is a condition recognized throughout the world, especially in Latin America, where the absence of control in the administration of unregulated substances for aesthetic purposes is evident, which has become an emerging problem due to the magnitude of complications, since some products, such as mineral oils, hydrocarbons, industrial silicone, generate serious consequences, both local and systemic, in the body. Many countries have not yet regulated the prohibition of this practice, although every day there are more campaigns to prevent it. However, at the same time the incidence of the disease increases worldwide due to the increase in these aesthetic procedures. In this regard, in Cuba, the growing number of people affected by this cause shows vulnerability in compliance with what has been established to date, that is why it is necessary to establish a legal framework of strict compliance that regulates the injection of modeling substances for aesthetic purposes.