Embryo development is impaired by sperm mitochondrial-derived ROS

BACKGROUND: Basal energetic metabolism in sperm, particularly oxidative phosphorylation, is known to condition not only their oocyte fertilising ability, but also the subsequent embryo development. While the molecular pathways underlying these events still need to be elucidated, reactive oxygen species (ROS) could have a relevant role. We, therefore, aimed to describe the mechanisms through which mitochondrial activity can influence the first stages of embryo development. RESULTS: We first show that embryo development is tightly influenced by both intracellular ROS and mitochondrial activity. In addition, we depict that the inhibition of mitochondrial activity dramatically decreases intracellular ROS levels. Finally, we also demonstrate that the inhibition of mitochondrial respiration positively influences sperm DNA integrity, most likely because of the depletion of intracellular ROS formation. CONCLUSION: Collectively, the data presented in this work reveals that impairment of early embryo development may result from the accumulation of sperm DNA damage caused by mitochondrial-derived ROS.

Golgi Transport 1A Promotes Cell Proliferation and Metastasis of Papillary Thyroid Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo investigate the expression level of Golgi transport 1A （GOLT1A） in thyroid carcinoma and its effects on the proliferation， migration， invasion， and epithelial-mesenchymal transition （EMT） of thyroid carcinoma cells. MethodsThe expression of GOLT1A in thyroid carcinoma was analyzed online by tumor immune estimation resource （TIMER）， the University of Alabama at Birmingham cancer data analysis portal （UALCAN）， gene expression profiling interactive analysis 2 （GEPIA2）. The expression level of GOLT1A in thyroid carcinoma cells was detected by real-time fluorescence quantitative polymerase chain reaction （RTFQ-PCR） and western blot. Cell counting kit-8 （CCK-8） assay， colony formation assay， and transwell assay were used to detect the effects of GOLT1A expression on the proliferation， migration， and invasion of thyroid carcinoma cells. Western blot assay was used to detect the effect of GOLT1A on the expression of EMT-related genes including E-cadherin， vimentin， and N-cadherin. ResultsThe online analysis of GEPIA2， TIMER， and UALCAN showed that the expression of GOLT1A was higher in thyroid carcinoma than in normal tissues， and the expression of GOLT1A in thyroid carcinoma cells was significantly higher than in normal control cells. Knockdown of GOLT1A inhibited TPC1 cell proliferation， migration， and invasion. The expression of E-cadherin increased and the expressions of N-cadherin and vimentin decreased in GOLT1A knockdown TPC1 cells. Overexpression of GOLT1A promoted BCPAP cell proliferation， migration， and invasion. The expression of E-cadherin decreased and the expressions of N-cadherin and vimentin increased in GOLT1A overexpression BCPAP cells. ConclusionGOLT1A is highly expressed in thyroid carcinoma and can promote the proliferation， migration， and invasion of thyroid carcinoma cells.

Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors / 药学学报

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

Research progress on the regulation of intestinal flora and effect on intestinal absorption and transport by TCM components / 药学实践杂志

The domestic and international research progress on the regulation of gut microbiota by Traditional Chinese Medicine (TCM) ingredients and their impact on intestinal absorption and transportation were summarized, which provided assistance for subsequent clinical rational drug use targeting gut microbiota. Literature on the relationship between gut microbiota and intestinal absorption and transportation in recent years were reviewed and analyzed, and the mechanism of TCM ingredients regulating gut microbiota on drug absorption and transportation was elucidated. Research has found that TCM ingredients alter gut microbiota, thereby affecting intestinal barrier function and absorption of transport proteins, which is of great significance for rational clinical medication.

Escala de Respuestas Emocionales por Estrés al Traslado en Transporte Público / Scale of Emotional Responses due to Commuting Stress in Public Transport

Resumen El traslado cotidiano entre la casa y el trabajo demanda un importante uso de recursos personales y puede llegar a ser estresante. El objetivo fue construir y evaluar una escala de respuestas emocionales por el estrés en el traslado en transporte público para la Zona Metropolitana del Valle de México de manera exploratoria. Método: Se realizó un estudio cualitativo a través de entrevistas semi estructuradas con el propósito de identificar emociones asociadas a la experiencia de estrés por el traslado para desarrollar los reactivos de acuerdo con el contexto. Posteriormente, dos estudios cuantitativos permitieron evaluar las propiedades psicométricas. Participaron 196 y 298 personas respectivamente. La aplicación de la escala se realizó en línea en septiembre de 2020 y abril de 2021. Resultados: la escala incluyó 26 respuestas emocionales asociadas al estrés. En el Análisis Factorial Exploratorio se redujo a nueve emociones negativas (X2=1183, gl=36, p=.001, KMO=.94, 60% de varianza explicada, Alfa ordinal=.93), corroboradas en el Análisis Factorial Confirmatorio (X2=41.87, gl=26, X2/gl=1.61, p=.025; RMR=.036, SRMR=.036, RMSEA=.045; GFI=.997, CFI=.999, TLI=.998). Conclusión: la propuesta exploratoria de la escala para evaluar las respuestas emocionales por el estrés en el traslado presenta valores adecuados para aplicarse en la Zona Metropolitana del Valle de México.

Abstract The stress in urban settings is related to a greater request for personal resources to face situations of daily life, such as the commuting, since in big cities, people spend a lot of time on it, and sometimes is uncomfortable and annoying, which can cause stress. Commuting stress has been assessed, through commuting daily hassles, commuting stressful features and physiological responses, but it is possible assess it through emotional responses. The aim of this study was to develop and assess an exploratory scale of emotional responses for the study of commuting stress by public transport in an urban area of México that is densely populated. Method, a cross sectional design was used, in which a qualitative exploratory study was carried out through 23 individual semi-structured interviews and two focus group, where it was identified the main emotions experienced during the commuting stress to develop the items in the language of the population. Subsequently, those emotions were compared with emotions proposed in previous studies to complement the scale. Thus, 26 emotions were included to assess the commuting stress through emotional responses. Finally, two quantitative studies were carried out to assess the psychometric properties of the scale, in which 196 and 298 people participated, respectively. The scale was applied online in September 2020 and in April 2021. Results, from the 26 emotional stress responses were reduced to nine negative emotions in an Exploratory Factor Analysis (X2=1183, df=36, p=.001, KMO= .94, 60% variance, Alfa ordinal=.93). This solution was corroborated with a Confirmatory Factor Analysis (X2=41.87, d.f.=26, X2/d.f.=1.61, p=.025; RMR= .036, SRMR=.036, RMSEA=.045; GFI=.997, CFI=.999, TLI=.998). Conserve only nine negative emotions is due to statistical analysis but also because some emotions referred to conditions of physical exhaustion or body energy level. On the other hand, positive emotions were related with pleasant commuting situations, not with the commuting stress experience. Conclusion, the exploratory scale to assess the commuting stress through emotional responses presents acceptable values to be applied in this urban area of Mexico.

Evaluación de la capacidad de centrado y transporte apical de los sistemas Reciproc Blue y XP-endo Shaper / Evaluation of the centering and apical transport capacity of Reciproc Blue and XP-endo Shaper systems

Resumen Objetivo: Comparar la capacidad de centrado y el transporte apical de los sistemas Reciproc Blue y XP-endo Shaper en bloques de resina con fotografías pre y posoperatorias yuxtapuestas, mediante un programa de análisis de imágenes. Materiales y Métodos: Se dividieron al azar 20 tacos de resina en dos grupos (n=10) preparados con XP-endo Sha- per y Reciproc Blue respectivamente. Se tomaron fotografías digitales de los tacos, antes y después de la preparación con cada sistema en una misma posición. Luego las fotografías obtenidas fueron yuxtapuestas mediante el software Photo shop. Se midieron las desviaciones del centro del conducto con respecto a la pared interna y externa del mismo en diversos puntos de referencia preestablecidos. Estos datos fueron analizados estadísticamente con el test de ANOVA. Resultados: Ambos sistemas produjeron transporte y desviación respecto a la trayectoria original del conducto radicular, pero el análisis estadístico (ANOVA Factorial 2x8) no cuantificó diferencias significativas entre ambos sistemas (p=0,4044) Conclusiones: Bajo las condiciones de este trabajo, ambos sistemas producen transporte y desviación respecto a la trayectoria original del conducto radicular.

Abstract Aim: To compare the centering capacity and apical transport of the Reciproc Blue and X-Pendo Shaper system in resin blocks with juxtaposed pre and postoperative photographs, using the Photoshop software. Materials and methods: 20 resin plugs were randomly divided into two groups (n=10) that were prepared with XP-endo Shaper and Reciproc Blue respectively. Digital photographs of the blocks were taken, before and after preparation, with each system in the same position. Then the obtained photographs were juxtaposed using Photoshop software. The deviations of the center of the canal, with respect to its inter nal and external wall, were measured at various pre-established reference points. These data were statistically analysed with the ANOVA test. Results: Both systems produced transport and deviation from the original trajectory of the root canal, but the statistical analysis (2x8 Factorial ANOVA) did not quantify significant differences between both systems (p=0.4044) Conclusions: Under the conditions of this work, both systems produce transport and deviation with respect to the original trajectory of the root canal.

Elexacaftor/tezacaftor/ivacaftor-real-world clinical effectiveness and safety. A single-center Portuguese study / Elexacaftor/tezacaftor/ivacaftor-efetividade clínica e segurança no mundo real. Estudo unicêntrico português

ABSTRACT Objective: To evaluate the effectiveness of treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) and to characterize its safety profile in cystic fibrosis (CF) patients in a real-world clinical setting. Methods: This was a prospective observational study carried out in a CF referral center in Portugal involving adult CF patients who started treatment with ELX/TEZ/IVA. Clinical characteristics of the patients were collected, and effectiveness and safety data were evaluated. Results: Of the 56 patients followed in the center at the time of the study, 28 were eligible for ELX/TEZ/IVA treatment in accordance with the Portuguese National Authority for Medicines and Health Products at the time of the study. Of these, 24 met the follow-up time requirement to be included in the clinical effectiveness analysis. The mean follow-up time was 167.3 ± 96.4 days. Adverse events were generally mild and self-limited. Significant improvements in lung function, BMI, sweat chloride concentration, and number of pulmonary exacerbations were observed. No significant differences in outcomes between F508del homozygous and heterozygous patients were found. The effectiveness of this new CFTR modulator combination also applied to patients with advanced lung disease. Conclusions: Treatment with ELX/TEZ/IVA showed effective improvement in real-world clinical practice, namely in lung function, BMI, sweat chloride concentration, and number of pulmonary exacerbations, with no safety concerns.

RESUMO Objetivo: Avaliar a efetividade do tratamento com elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) e caracterizar seu perfil de segurança em pacientes com fibrose cística (FC) em um cenário clínico de mundo real. Métodos: Estudo observacional prospectivo realizado em um centro de referência em FC de Portugal com pacientes adultos com FC que iniciaram o tratamento com ELX/TEZ/IVA. As características clínicas dos pacientes foram coletadas, e os dados de efetividade e segurança, avaliados. Resultados: Dos 56 pacientes acompanhados no centro na época do estudo, 28 eram elegíveis para o tratamento com ELX/TEZ/IVA de acordo com a Autoridade Nacional do Medicamento e Produtos de Saúde. Destes, 24 atenderam ao requisito de tempo de acompanhamento para inclusão na análise de efetividade clínica. O tempo médio de acompanhamento foi de 167,3 ± 96,4 dias. Os eventos adversos foram geralmente leves e autolimitados. Foram observadas melhoras significativas na função pulmonar, no IMC, na concentração de cloreto no suor e no número de exacerbações pulmonares. Não foram encontradas diferenças significativas nos resultados entre os pacientes homozigotos e heterozigotos para F508del. A efetividade dessa nova combinação de moduladores da CFRT em fibrose cística também se aplica a pacientes com doença pulmonar avançada. Conclusões: O tratamento com ELX/TEZ/IVA demonstrou melhora efetiva na prática clínica real, a saber, na função pulmonar, no IMC, na concentração de cloreto no suor e no número de exacerbações pulmonares, sem preocupações de segurança.

Competencies for aeromedical evacuation practices in emergencies and disasters: a scoping review / Competencias para prácticas de evacuación aeromédica en emergencias y desastres: revisión del alcance / Competências para práticas de evacuações aeromédicas em emergências e desastres: revisão de escopo

ABSTRACT Objective: to map the competencies developed in training strategies for air transport practices for patients, in the face of emergency situations and disasters involving chemical, biological, radiological and nuclear (CBRN) agents. Method: this is a scoping review structured in accordance with the JBI and Preferred Reporting Items for Systematic reviews and Metanalyses extension for Scoping Reviews recommendations. The study was carried out in five stages: search for sources in 17 databases, an information portal and two repositories of gray literature, using 125 DeCS, MeSH and Emtree descriptors, without temporal and idiomatic clipping; selection; critical reading of the texts selected by two double-blind reviewers; summary of results and presentation of mapped competencies. Results: a total of 878 studies were analyzed, of which 18 composed the sample. In all, 11 competencies were mapped, with emphasis on the technical training domain. Competencies refer especially to technical-scientific knowledge in disaster situations involving CBRN agents and the safety of patients and professionals involved. Conclusion: the operationalization of artifices to improve qualification processes based on competencies proved to be strategic to increase the quality and safety of patient air transport practices. The approach of the sources on specific aspects of the particularities of practices related to emergencies and disasters involving CBRN agents in training/training processes demonstrates the academic effort to promote the reduction of the risk of these events when, in due course, civil and military institutions and their health operators are activated.

RESUMEN Objetivo: mapear las competencias desarrolladas en estrategias de formación en prácticas de transporte aéreo de pacientes, ante situaciones de emergencia y desastres con agentes químicos, biológicos, radiológicos y nucleares (QBRN). Método: una revisión de alcance estructurada de acuerdo con las recomendaciones del JBI y la lista de verificación Elementos de informe preferidos para revisiones sistemáticas y la extensión Metanalyses para revisiones de alcance. El estudio se realizó en cinco etapas: búsqueda de fuentes en 17 bases de datos, un portal de información y dos repositorios de literatura gris, utilizando 125 descriptores DeCS, MeSH y Emtree, sin recorte temporal e idiomático; selección; lectura crítica de los textos seleccionados por dos revisores doble ciego; resumen de resultados y presentación de competencias mapeadas. Resultados: se analizaron 878 estudios, de los cuales 18 compusieron la muestra. En total, se mapearon 11 competencias, con énfasis en el dominio de formación técnica. Las competencias se refieren especialmente al conocimiento técnico-científico en situaciones de desastres que involucran a agentes QBRN y la seguridad de los pacientes y profesionales involucrados. Conclusión: la operacionalización de artificios para mejorar los procesos de calificación basados ​​en competencias demostró ser estratégica para aumentar la calidad y seguridad de las prácticas de transporte aéreo de pacientes. El abordaje de las fuentes sobre aspectos específicos de las particularidades de las prácticas relacionadas con emergencias y desastres que involucran a agentes QBRN en los procesos de formación/capacitación demuestra el esfuerzo académico por promover la reducción del riesgo de estos eventos cuando, en su momento, se activan las instituciones civiles y militares y sus operadores de salud.

RESUMO Objetivo: mapear as competências desenvolvidas em estratégias de capacitação para práticas de transporte aéreo de pacientes, diante de situações de emergência e desastres envolvendo agentes químicos, biológicos, radiológicos e nucleares (QBRN). Método: revisão de escopo estruturada conforme as recomendações do Joanna Briggs Institute e do checklist Preferred Reporting Items for Systematic reviews and Metanalyses extension for Scoping Reviews. O estudo foi desenvolvido em cinco etapas: busca de fontes em 17 bases de dados, um portal de informação e dois repositórios de literatura cinzenta, utilizando 125 descritores DeCS, MeSH e Emtree, sem recorte temporal e idiomático; seleção; leitura crítica na íntegra dos textos selecionados por dois revisores em duplo cego; síntese dos resultados e apresentação das competências mapeadas. Resultados: foram analisados 878 estudos, dos quais 18 compuseram a amostra. Ao todo, foram mapeadas 11 competências, com destaque para o domínio capacitação técnica. As competências referem-se especialmente ao conhecimento técnico-científico em situações de desastre envolvendo agentes QBRN e à segurança do paciente e dos profissionais envolvidos. Conclusão: a operacionalização de artifícios para aperfeiçoar os processos de capacitação baseados em competências mostrou-se estratégica para elevar a qualidade e a segurança das práticas de transporte aéreo de pacientes. A abordagem das fontes sobre aspectos específicos das particularidades das práticas relacionadas às emergências e desastres envolvendo agentes QBRN em processos de formação/capacitação demonstra o esforço acadêmico de promover a redução do risco desses eventos quando, oportunamente, forem acionadas instituições civis e militares e seus operadores de saúde.

Immunoexpression profile of hypoxia-inducible factor (HIF) targets in potentially malignant and malignant oral lesions: a pilot study

Abstract Oral potentially malignant disorders (OPMD) are associated with an increased risk of oral squamous cell carcinoma (OSCC). OSCC has an aggressive profile and is the most prevalent among different head and neck malignancies. Most OSCC patients are diagnosed with advanced stage tumors and have a poor prognosis. Cancer cells are able to reprogram their metabolism, even in the presence of oxygen, enhancing the conversion of glucose to lactate via the glycolytic pathway, a phenomenon mainly regulated by hypoxia-inducible factor (HIF) signaling. Thus, several glycometabolism-related biomarkers are upregulated. Objectives This study aimed to evaluate the immunoexpression of the HIF targets GLUT1, GLUT3, HK2, PFKL, PKM2, pPDH, LDHA, MCT4, and CAIX in OPMD and OSCC samples, in order to identify potential correlations between biomarkers' immunoexpression, clinicopathological features, and prognostic parameters. Methodology OSCC and OPMD samples from 21 and 34 patients (respectively) were retrospectively collected and stained for the different biomarkers by immunohistochemistry. Results CAIX and MCT4 expressions were significantly higher in OSCC samples when compared with OPMD samples, while the rest were also expressed by OPMD. GLUT3 and PKM2 alone, and the concomitant expression of more than four glycometabolism-related biomarkers were significantly correlated with the presence of dysplasia in OPMD. When considering OSCC cases, a trend toward increased expression of biomarkers and poor clinicopathological features was observed, and the differences regarding HK2, PFKL, LDHA and MCT4 expression were significant. Moreover, HK2 and CAIX were correlated with low survival rates. GLUT1 and GLUT3 were significantly associated with poor outcome when their expression was observed in the hypoxic region of malignant lesions. Conclusion OPMD and OSCC cells overexpress glycolysis-related proteins, which is associated with aggressive features and poor patient outcome. Further research is needed to deeply understand the glycolic phenotype in the process of oral carcinogenesis.

Use of elexacaftor+tezacaftor+ivacaftor in individuals with cystic fibrosis and at least one F508del allele: a systematic review and meta-analysis / Uso de elexacaftor + tezacaftor + ivacaftor em indivíduos com fibrose cística com pelo menos um alelo F508del: revisão sistemática e meta-análise

ABSTRACT Objective: To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor (ETI)-on important clinical endpoints in individuals with cystic fibrosis. Methods: This was a systematic review and meta-analysis of randomized clinical trials that compared the use of ETI in individuals with CF and at least one F508del allele with that of placebo or with an active comparator such as other combinations of CFTR modulators, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) methodology. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to December 26th, 2022. The risk of bias was assessed using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: We retrieved 54 studies in the primary search. Of these, 6 met the inclusion criteria and were analyzed (1,127 patients; 577 and 550 in the intervention and control groups, respectively). The meta-analysis revealed that the use of ETI increased FEV1% [risk difference (RD), +10.47%; 95% CI, 6.88-14.06], reduced the number of acute pulmonary exacerbations (RD, −0.16; 95% CI, −0.28 to −0.04), and improved quality of life (RD, +14.93; 95% CI, 9.98-19.89) and BMI (RD, +1.07 kg/m2; 95% CI, 0.90-1.25). Adverse events did not differ between groups (RD, −0.03; 95% CI, −0.08 to 0.01), and none of the studies reported deaths. Conclusions: Our findings demonstrate that ETI treatment substantially improves clinically significant, patient-centered outcomes.

RESUMO Objetivo: Avaliar o efeito do tratamento com a combinação de três moduladores da proteína cystic fibrosis transmembrane conductance regulator (CFTR, reguladora de condutância transmembrana em fibrose cística) - elexacaftor + tezacaftor + ivacaftor (ETI) - sobre desfechos clínicos importantes em indivíduos com fibrose cística. Métodos: Revisão sistemática e meta-análise de ensaios clínicos randomizados que compararam o uso de ETI em indivíduos com fibrose cística com pelo menos um alelo F508del com o uso de placebo ou de um comparador ativo como outras combinações de moduladores da CFTR. O estudo foi realizado seguindo as recomendações Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) e a metodologia Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO). Foram realizadas buscas nos seguintes bancos de dados: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials e ClinicalTrials.gov, desde a sua criação até 26 de dezembro de 2022. O risco de viés foi avaliado por meio da ferramenta de risco de viés da Cochrane, e a qualidade das evidências foi determinada com base no sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). Resultados: Foram identificados 54 estudos na busca primária. Destes, 6 preencheram os critérios de inclusão e foram analisados (1.127 pacientes: 577 pacientes intervenção e 550 pacientes controle). A meta-análise revelou que o uso de ETI aumentou o VEF1 em porcentagem do previsto [diferença de risco (DR): +10,47%; IC95%: 6,88-14,06], reduziu o número de exacerbações pulmonares agudas (DR: −0,16; IC95%: −0,28 a −0,04) e melhorou a qualidade de vida (DR: +14,93; IC95%: 9,98-19,89) e o IMC (DR: +1,07 kg/m2; IC95%: 0,90-1,25). Os eventos adversos não diferiram entre os grupos (DR: −0,03; IC95%: −0,08 a 0,01), e nenhum dos estudos relatou óbitos. Conclusões: Nossos achados demonstram que o tratamento com ETI melhora substancialmente os desfechos clinicamente significativos centrados no paciente.

Efecto del ácido deoxicólico sobre la regulación del transporte iónico intestinal en la rata / Deoxycholic acid efect on intestinal ionic transport regulation in the rat

The intestine has a very important role in the homeostasis of the internal medium. Bile acids play a regulatory role in the digestion and absorption of nutrients. Among them, deoxycholic acid, when its luminal concentration increases due to bacterial overgrowth, modifies hydroelectrolytic transport, producing an increase in the volume of water and electrolytes in stools.

El intestino tiene un papel muy importante en la homeostasis del medio interno. Los ácidos biliares cumplen una función reguladora en la digestión y absorción de nutrientes. Entre ellos el ácido deoxicólico, cuando aumenta su concentración luminal por sobrecrecimiento bacteriano, modifica el transporte hidroelectrolítico produciendo aumento del volumen de agua y electrolitos en las deposiciones.

Sexual harassment in public transport among female students at the Federal university of technology Akure, Nigeria

Background: Every day females experience different types of sexual harassment while using public transportation worldwide. Objective: This study aims to determine the prevalence of sexual harassment amongst female students who travel by public transportation at the Federal University of Technology Akure (FUTA) Nigeria. Materials and Methods: A cross-sectional descriptive study. Data was collected using electronic questionnaires and analyzed with IBM SPSS Statistics version 21. Frequencies and percentages were used for data summary. Association between variables was determined using Chi Square test. Statistical significance was a p-value < 0.05. Results: Ninety-three percent of female students in FUTA had experienced sexual harassment. Among those who had experienced sexual harassment, 98.4% were single, 81.5% lived off campus, 79.0% used public bus, 45.4% commuted daily, 84.7% was in an overcrowded vehicle and 52.9% was in the evening. There was a significant association between sexual harassment and marital status (p = 0.033), place of residence (p = 0.019), mode of public transportation (p = 0.014), time of travel (p = 0.018). Verbal sexual harassment was most prevalent (91.1%), followed by physical sexual harassment (87.6%) and non-verbal sexual harassment (82%). Conclusion: This study found a high prevalence of sexual harassment among female university students in FUTA using public transportation, which occurs in a variety of scenarios, particularly in crowded vehicles during rush hour

Leptospiral c-di-AMP-binding protein regulates potassium ion transport / 中华微生物学和免疫学杂志

Objective:To investigate whether KtrA was a binding protein of c-di-AMP, the second messenger in Leptospira, and to explore the function and regulatory mechanism of the c-di-AMP-KtrA/B system. Methods:KtrA gene was amplified by PCR and cloned into pET42a plasmid to construct the pET42a ktrA prokaryotic expression vector. Then the vector was transferred into E. coli BL21DE3 to construct an engineering bacterium E. coli BL21DE3 pET42a-ktrA for the expression of recombinant KtrA (rKtrA). The expressed rKtrA was purified by affinity chromatography. BIAcore technology was used to detect the binding ability of rKtrA to c-di-AMP. Bacterial two-hybrid analysis was used to analyze the interaction between KtrA and KtrB in the leptospiral Ktr system with or without exogenetic c-di-AMP. The above genes were then complemented into the potassium transport-deficient E. coli mutants to analyze the function of the c-di-AMP-KtrA/B pathway. Results:An prokaryotic engineering bacterium for the expression of ktrA gene of Leptospira was constructed successfully. The purified rKtrA could specifically bind to c-di-AMP. There was interaction between KtrA and KtrB, but the interaction could be dissociated by c-di-AMP. The KtrA/B system was involved in potassium ion uptake and it was negatively regulated by c-di-AMP. Conclusions:Leptospiral KtrA was a c-di-AMP-binding protein and the c-di-AMP-KtrA/B system was involved in potassium ion transport.

Role of activation of VGLUT2 neurons in vagal nodose ganglion in dexmedetomidine-caused bradycardia in mice / 中华麻醉学杂志

Objective:To evaluate the role of activation of vesicular glutamate transporter 2 (VGLUT2) neurons in vagal nodose ganglion in dexmedetomidine-caused bradycardia in mice.Methods:Ninety-six SPF healthy male VGLUT2-cre mice, aged 10 weeks, weighing 20-25 g, were divided into 6 groups ( n=16 each) by the random number table method: normal saline control group (NS group), dexmedetomidine group (Dex group), viral control + chemogenetic control + dexmedetomidine group (eGFP-NS+ Dex group), viral transfection + chemogenetic control + dexmedetomidine group (hM4Di-NS+ Dex group), viral control + chemogenetic inhibition + dexmedetomidine group (eGFP-CNO+ Dex group) and viral transfection + chemogenetic inhibition + dexmedetomidine group (hM4Di-CNO+ Dex group). Dexmedetomidine 100 μg/kg was intraperitoneally injected in Dex group. The equal volume of normal saline was intraperitoneally injected in NS group. AAV2/9-hSyn-DIO-hM4Di-eGFP was injected in the right nodose ganglion in hM4Di-NS+ Dex group and hM4Di-CNO+ Dex group, and AAV2/9-hSyn-DIO-eGFP was injected in the right nodose ganglion in eGFP-NS+ Dex group and eGFP-CNO+ Dex group, allowing the virus expression for 21 days. On the 22nd day after virus injection, clozapine-n-oxide (CNO) 5 mg/kg was intraperitoneally injected in hM4Di-CNO+ Dex group and eGFP-CNO+ Dex group, the equal volume of normal saline was intraperitoneally injected in hM4Di-NS+ Dex group and eGFP-NS+ Dex group, 1 h later the efficacy of CNO reached the peak, and then dexmedetomidine 100 μg/kg was intraperitoneally injected. The respiratory rate, heart rate, SpO 2 and discharge frequency of the right vagal nodose ganglion were synchronously measured by multi-channel electrophysiology in vivo. The expression of phosphorylated extracellular signal-regulated kinase (pERK) and VGLUT2 and co-expression of pERK and VGLUT2 in the right vagal nodose ganglion were detected by immunofluorescence assay. Results:Compared with NS group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in the other five groups ( P<0.05). Compared with Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly decreased, and pERK expression was down-regulated in hM4Di-CNO+ Dex group, and no significant change was found in the parameters mentioned above in hM4Di-NS+ Dex group, eGFP-NS+ Dex group and eGFP-CNO+ Dex group ( P>0.05). Compared with hM4Di-CNO+ Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in eGFP-CNO+ Dex group ( P<0.05). There was no significant difference in the percentage of respiratory variation and SpO 2 among the six groups ( P>0.05). The expression of VGLUT2-positive neurons was abundant in nodose ganglia, and the co-expression rate of pERK and VGLUT2 was nearly 90%. The co-expression rate of pERK and VGLUT2 decreased to about 30% after inhibition of VGLUT2 neurons in ganglion. Conclusions:The mechanism by which dexmedetomidine causes bradycardia is associated with activation of VGLUT2 neurons in vagal nodose ganglia in mice.

Automatic radiolabeling of the norepinephrine transporter targeted tracer 18F-mFBG and evaluation of 18F-mFBG PET/CT imaging in pheochromocytoma / 中华核医学与分子影像杂志

Objective:To fulfill the automatic radiolabeling of the norepinephrine transporter (NET) trancer 18F-meta-fluorobenzylguanidine (mFBG), and explore the 18F-mFBG PET/CT imaging effect of pheochromocytoma. Methods:On the basis of the chemical structure of mFBG, a spirocyclic iodonium ylide was used as the precursor to undergo a 3-step reaction sequence (radiofluorination, deprotection and neutralization) on AllinOne synthesis module. Purification by high performance liquid chromatography and formulation were conducted to generate 18F-mFBG. The corresponding quality control tests of 18F-mFBG product was performed. Afterwards, a postoperative patient with pheochromocytoma underwent 18F-mFBG PET/CT imaging. Results:The radiosynthesis was accomplished within 70 min, and 18F-mFBG was obtained in (17.8±2.4)% non-decay-corrected radiochemical yield ( n=5), with radiochemical purity >97% and molar activity >59.2 GBq/μmol. Sterility test, bacterial endotoxins test, abnormal toxicity test and the acetonitrile residue all met the requirements of Pharmacopoeia of the People′ s Republic of China (2020 Volume Ⅳ). The 18F-mFBG PET/CT imaging disclosed high uptake in pheochromocytoma and clear localization of lesions. Conclusions:The automatic radiolabeling of the NET targeted tracer 18F-mFBG is successfully realized by commercially available synthesis module, and the production quality meets all requirements for clinical translation. 18F-mFBG has a potential to image neuroendocrine lesions in clinical setting.

Establishment and clinical verification of brain template for analyzing 11C-CFT PET imaging data / 中华核医学与分子影像杂志

Objective:To establish standard spatial brain template and ROIs template of 11C-methyl- N-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) PET images for automated quantitative analysis of dopamine transporter (DAT) distribution. Methods:From May 2014 to December 2015, 11C-CFT PET and MRI T 1 brain images of 16 healthy volunteers (3 males, 13 females; age (63.3±6.9) years) from Huashan Hospital, Fudan University were co-registered and smoothed using statistical parametric mapping(SPM)5 software based on MATLAB to create a standard spatial brain template. The ROIs template was established by ScAnVp procedures. These templates were clinically verified by using 11C-CFT PET images of 37 healthy volunteers (23 males, 14 females; age (61.7±7.1) years), 32 Parkinson′s disease (PD) patients (20 males, 12 females; age (61.1±5.4) years), 10 multiple system atrophy with predominant parkinsonism (MSA-P) patients (7 males, 3 females; age (60.8±7.1) years) and 10 progressive supranuclear palsy (PSP) patients (5 males, 5 females; age (58.4±6.1) years) from Huashan Hospital, Fudan University between January 2014 and March 2019. One-way analysis of variance was used to analyze data. Results:Based on the 11C-CFT PET images and MRI T 1 images of healthy volunteers, a standard spatial brain template for normalization of 11C-CFT PET images was created. The ROIs template was established including seven regions: bilateral caudate, anterior putamen, posterior putamen (along the long axis) and the occipital cortex. The ROIs template was accurately aligned in each verification group. The normal reference values of semi-quantitative DAT distribution in caudate, anterior putamen and posterior putamen were obtained (1.84±0.13, 2.18±0.16, 1.77±0.11). The semi-quantitative values of 11C-CFT uptake in each ROI in patients were significantly lower than those in healthy volunteers ( F values: 49.79-283.83, all P<0.05). Conclusion:The established brain templates with accurate spatial alignment for 11C-CFT image analysis can provide foundational tools for the application of 11C-CFT PET imaging in clinical practice and scientific research.

Study on the influencing factors and mechanism of cholesterol polyps and cholesterol calculus in gallbladder / 中华肝胆外科杂志

Objective:To explore the pathogenesis of gallbladder cholesteryl polyps (GCP) and gallbladder cholesterol calculus (GCC) by studying the different changes of mucin (MUC) expression and reverse cholesterol transporter (RCT) in gallbladder mucosa epithelium.Methods:The data of 10 GCP patients (GCP group), 10 GCC patients (GCC group) and 5 patients with normal gallbladder resection (control group) were retrospectively analyzed, who underwent cholecystectomy in the Department of General Surgery, Xuanwu Hospital, Capital Medical University from January to December 2021. Among the 10 patients in the GCP group, there were 5 males and 5 females, aged (43.40±9.59) years old. Among the 10 patients in the GCC group, 5 males and 5 female, aged (45.00±8.13) years old. Among the 5 patients in the control group, there were 3 males and 2 females, aged (43.80±6.01) years old. Immunohistochemical analysis was used to investigate the expression differences of various subtypes of MUC and RCT [ATP binding cassette transporter G1 (ABCG1) and B group type I scavenger receptor (SR-BI)] among each group.Results:Compared with the control group, the expression of MUC1 (3.40±0.70 vs. 0), MUC5AC (1.50±0.53 vs. 0), MUC6 (4.70±0.48 vs. 0), and ABCG1 (3.50±0.53 vs. 1.60±0.55) in the gallbladder mucosa of the GCP group increased, while the expression score of SR-BI decreased (1.70±0.48 vs. 3.40±0.55), with statistical significance (all P<0.001). Compared with the control group, the expression of MUC1 (4.80±0.42 vs. 0), MUC5AC (4.70±0.48 vs. 0), MUC6 (3.30±0.67 vs. 0), and ABCG1 (3.40±0.52 vs. 1.60±0.55) in the gallbladder mucosa of the GCC group increased, while the expression score of SR-BI decreased (0 vs. 3.40±0.55), with statistically significant differences (all P<0.001). Conclusion:The different expression levels of MUC1, MUC5AC, MUC6, and RCT proteins lead to the differential formation of GCP and GCC on the basis of the co-pathogenesis in high cholesterol in bile.

Tibial transverse bone transport assisted by nose ring drainage for treatment of foot and ankle chronic osteomyelitis / 中华创伤骨科杂志

Objective:To investigate the clinical effects of tibial transverse bone transport assisted by nose ring drainage (NRD) in the treatment of foot and ankle chronic osteomyelitis.Methods:A retrospective study was conducted to analyze the data of 32 patients with foot and ankle chronic osteomyelitis who had been treated at Department of Orthopedics, Beijing Rehabilitation Hospital from March 2013 to February 2022. The patients were assigned into a study group and a control group. In the control group, there were 12 males and 3 females, aged (39.5±8.8) years. The osteomyelitis was located at the distal tibia in 4 cases, at the talus in 1 case, at the calcaneus in 2 cases, at the midfoot in 4 cases and at the forefoot in 4 cases. According to the Crerny-Mader classification, there were 5 cases of type Ⅰ and 10 cases of type Ⅱ. The control group was treated with Ilizarov transverse tibial bone transport in combination with thorough debridement and anti-infection therapy. In the study group, there were 12 males and 5 females, aged (42.3±13.4) years. The osteomyelitis was located at the distal tibia in 4 cases, at the talus in 1 case, at the calcaneus in 3 cases, at the midfoot in 5 cases and at the forefoot in 4 cases. According to the Crerny-Mader classification, there were 7 cases of type Ⅰ and 10 cases of type Ⅱ. The study group was treated with NRD drainage in addition to the procedures in the control group. The curative effects were evaluated by comparing the cure, recurrence, amputation (toe amputation), antibiotic use time, wound healing time, relevant inflammatory indicators [WBC, neutrophil percentage (NEU), erythrocyte sedimentation rate (ESR), procalcitonin, interleukin-6 (IL-6), C-reactive protein (CRP)], and postoperative functional recovery between the 2 groups.Results:The 2 groups were comparable because there was no statistically significant difference in the general data between them ( P>0.05). The follow-up period was (36.0±9.8) months. There was no significant difference between the 2 groups in the cure or amputation (toe amputation) ( P>0.05), but the recurrence rate in the study group was significantly lower than that in the control group ( P<0.05). The antibiotic use time [(20.7±3.6) d] and wound healing time [(88.3±17.1) d] in the study group were significantly shorter than those [(37.9±6.5) d and (102.2±22.6) d] in the control group ( P<0.05). The ESR, IL-6 and CRP at 1 week after operation in the study group were significantly lower than those in the control group ( P<0.05), but there was no significant difference between the 2 groups in the WBC, NEU or PCT at 1 week after operation ( P>0.05). There was no significant difference either in the inflammatory indicators between the 2 groups at 1 month after operation ( P>0.05). In all patients, the inflammatory indicators like WBC, NEU, ESR, PCT, IL-6 and CRP at 1 week and 1 month after operation were significantly better than those before operation, and the Maryland foot functional score at 12 months after operation was significantly higher than the preoperative one ( P<0.05). There was no significant difference between the 2 groups in the Maryland foot functional score at 12 months after operation ( P>0.05). Conclusion:In the treatment of foot and ankle chronic osteomyelitis, compared with the Ilizarov transverse tibial bone transport, our tibial transverse bone transport assisted by NRD can achieve satisfactory therapeutic effects, shorten antibiotic use time and treatment cycle, and reduce recurrence rate.

Management of helicopter medical transport in 36 patients with critical cardiac disease / 中华危重病急救医学

Objective:To summarize the management experience of helicopter medical transport in patients with critical heart disease, so as to provide reference for transport of patients with critical heart disease under the background of major natural disasters.Methods:The clinical and transport data of 36 critically ill cardiac patients in Fuwai Central China Cardiovascular Hospital from 16:30 on July 21 to 19:30 on July 22, 2021 due to historically rare heavy rainstorms were collected. All 36 critically ill cardiac patients were transported by helicopter. The safe transportation was implemented under the measures of quickly forming a transport leadership and coordination group, clarifying responsibilities and division of labor, doing a good job in the pretreatment of the patient's condition, pipeline assessment and mechanical circulation support (MCS) equipment, simulating and practicing the transfer process, improving the safety of the transfer implementation process, and effectively handing over with the target hospital. The gender, age, disease type, MCS, transport and outcome of patients were collected.Results:Thirty-six patients with cardiac critical illness were from adult extracardiac intensive care unit (ICU), adult cardiac care unit (CCU), children's CCU, comprehensive ICU and department of neurology. There were 24 males and 12 females; age (50.93±20.86) years old. There were 12 patients using respirator, 7 patients needing MCS, 2 of whom needed both extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pump (IABP), and 7 patients with post-cardiac surgery. The total distance of transportation of 36 patients was 1 638.4 km, the transit time was 10.5 hours, one way flight time of helicopter was about 8 minutes, and the average transport time per patient was about 17.5 minutes. The vital signs of 36 patients during transport were basically stable, without complications, and all of them reached the target hospital safely.Conclusion:Under the seamless connection of the rapid establishment of the transfer leadership coordination group, assessment of the patient's condition and pretreatment, the simulation of the transfer process, and the effective handover with the receiving hospital, the use of helicopter for medical transport for critically ill heart patients is feasible and safe, which can buy valuable time for saving patients' lives and further treatment.

Research progress on sex hormone-binding globulin involved in the occurrence and development of diabetes mellitus / 中国基层医药

Sex hormone-binding globulin (SHBG) is significantly associated with abnormal glucose metabolism. Low SHBG level is a risk factor for insulin resistance and the occurence of diabetes mellitus. SHBG is negatively correlated with the risk of type 2 diabetes mellitus and plays an important role in regulating insulin resistance while predicting its development. The genotype of SHBG has been found to be closely related to the occurrence of diabetes mellitus. Fatty liver and DNA methylation are also important factors mediating the relationship between SHBG and type 2 diabetes mellitus. The change in SHBG level may be related to insulin resistance by influencing hepatocyte nuclear factor 4a and regulating glucose transporter.