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Objective: To observe the changes of lung function and inflammatory factors in rat models of coal workers' pneumoconiosis at different time points. Methods: In June 2021, 96 healthy male SD rats with SPF grade were divided into 1, 3, and 6-month control group and dust staining group (coal dust group, coal silica dust group, quartz group) according to random number table method, with 8 rats in each group. After one week of adaptive feeding, a one-time non-exposed tracheal perfusion method (1 ml/ piece) was used. The dust dyeing group was given 50 g/L coal dust, coal silica mixed dust and quartz dust suspension, respectively, and the control group was given 0.9% normal saline solution. At 1, 3 and 6 months after perfusion, lung function was detected by animal lung function apparatus, then all lung tissues and alveolar lavage fluid were killed, and lung histopathological morphological changes were observed by HE staining, and the contents of interleukin (IL-1ß), IL-18, IL-4 and IL-10 in alveolar lavage fluid were detected by ELISA. One-way analysis of variance was used to compare groups. Two factors (inter-group treatment factor (4 levels) and observation time factor (3 levels) ) were used in the analysis of the effects of inter-group treatment and treatment time on related indicators. Results: HE staining results showed that coal spot appeared in the lung tissue of coal dust group, coal spot and coal silicon nodule appeared in the lung tissue of coal dust group, and silicon nodule appeared in the lung tissue of quartz group. Compared with the control group, the forced vital capacity (FVC) and forced expiratory volume at 0.2 second (FEV(0.2)) of rats in the dust staining group had interaction between the treatment and treatment time (P<0.05). With the increase of dust dyeing time, FVC and FEV(0.2) decreased significantly at 3-6 months of dust dyeing, and the maximum gas volume per minute (MVV) decreased significantly at 1-3 months of dust dyeing (P<0.05). The lowest lung function index was in quartz group, followed by coal-silica group and coal-dust group. There were statistically significant differences in the main effect and interaction effect of the pro-inflammatory factor IL-18 among all groups in treatment and treatment time (IL-18: F=70.79, 45.97, 5.90, P<0.001), and interaction existed. The highest content of inflammatory factors in alveolar lavage fluid of all dust groups was quartz group, followed by coal silica group and coal dust group. There were significant differences in the main effect and interaction effect of anti-inflammatory factors between groups and treatment time (IL-4: F=41.55, 33.01, 5.23, P<0.001, <0.001, <0.001; IL-10: F=7.46, 20.80, 2.91, P=0.002, <0.001, 0.024), and there was interaction. The highest content of anti-inflammatory factor was in quartz group, followed by coal silica group and coal dust group. Conclusion: Lung function decreased and levels of inflammatory fators increased in rat models of coal workers' pneumoconiosis, with the quartz group being the most severely damaged. Lung function is mainly impaired in thrid-six months, and the content of inflammatory factors begins to change in first-thrid months. MVV are the earliest and most obvious in lung function. IL-18 is suitable for monitoring changes in the pro-inflammatory response of coal workers' pneumoconiosis, and IL-10 is suitable for monitoring changes in anti-inflammatory response.
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Antracosis , Carbón Mineral , Modelos Animales de Enfermedad , Polvo , Pulmón , Ratas Sprague-Dawley , Animales , Ratas , Masculino , Pulmón/fisiopatología , Pulmón/patología , Antracosis/fisiopatología , Interleucina-18/metabolismo , Interleucina-4/metabolismo , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Líquido del Lavado Bronquioalveolar/citología , Cuarzo , Inflamación , Pruebas de Función RespiratoriaRESUMEN
Objective: To understand the occupational stress and mental health status of hospital infection prevention and control practitioner (HIPCPs) in medical institutions, and analyze their main influencing factors. Methods: In November 2021, 550 nosocomial infection managers in Tianjin were randomly selected to conduct a questionnaire survey using the Concise Occupational Stress Questionnaire, Depression Screening Scale (PHQ-9) and Self-Rating Anxiety Scale (SAS). 497 valid questionnaires were obtained, and the total recovery efficiency was 90.36%. Single factor analysis and multivariate logistic regression method were used to analyze the main influencing factors of occupational stress and mental health status of psychiatric managers. Results: The detection rate of anxiety and depression among 497 HIPCPs was 22.73% (113/497) and 58.95% (293/497), respectively. Gender and major were the influencing factors of depression (P=0.000, 0.001). Average working hours>52 hours per week and night shift days>1 days per week were the influencing factors of anxiety (P=0.035, 0.014). Average working hours>52 h per week, night shift days >1 d per week and different majors were the influencing factors of occupational stress (P=0.000, 0.025, 0.010). Multivariate logistic regression results showed that the risk of anxiety in those who worked more than 52 hours per week was 1.753 times that of those who worked less than 52 hours per week (P=0.038), and the risk of depression in women was 3.071 times that of men (P=0.006) . Conclusion: Working hours are an important influencing factor for occupational stress and anxiety among HIPCPs. In order to reduce the occurrence of occupational stress and mental health problems, it is necessary to strengthen psychological counseling for HIPCPs and balance work and rest.
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Ansiedad , Depresión , Estrés Laboral , Humanos , Masculino , Femenino , Encuestas y Cuestionarios , Depresión/epidemiología , Depresión/psicología , Ansiedad/epidemiología , Adulto , Estrés Laboral/psicología , Estrés Laboral/epidemiología , Infección Hospitalaria/prevención & control , Infección Hospitalaria/epidemiología , Salud Mental , China/epidemiología , Análisis Multivariante , Persona de Mediana Edad , Modelos LogísticosRESUMEN
Objective: To explore the clinical phenotypes and pathogenic gene variation characteristics of three Chinese Han ethnic families affected by Nance-Horan syndrome, a rare X-linked genetic disorder. Methods: A pedigree investigation study was conducted at the First Affiliated Hospital of Zhengzhou University, collecting clinical data from three Chinese Han families with Nance-Horan syndrome between February 2009 and September 2018. Detailed family histories, comprehensive ophthalmological and systemic examinations were documented. Pedigree charts were created, and genetic inheritance patterns were analyzed to preliminarily diagnose the probands and other affected individuals. Genomic DNA was extracted from peripheral blood samples of family members, and next-generation sequencing was used to screen for target gene variations, which were confirmed by Sanger sequencing. Pathogenicity of the genetic variants and their impact on three-dimensional protein structure were analyzed using MutationTaster and computer-aided protein modeling. Results: In Family 1, there are 5 patients, including 4 females (aged 42, 37, 9 and 7) and 1 males (aged 12). In Family 2, there are 5 patients, including 3 females (aged 54, 32 and 16) and 2 males (aged 26 and 9). In Family 3, there are 8 patients, including 5 females (aged 69, 42, 37, 35 and 14) and 3 males (aged 10, 7 and 4). All probands in the three families exhibited nuclear cataracts with typical congenital hereditary cataract features, but no noticeable abnormalities in facial appearance or teeth. Next-generation sequencing identified new variation sites in the NHS gene, specifically c.2519_2520del, exon3del, and c.3847C>T. These variations included nonsense mutation p.(Ser840*), exon deletion p.(?), and nonsense mutation p.(Gln1283*). Combined clinical and genetic sequencing results confirmed X-linked Nance-Horan syndrome in all three families. Bioinformatics analysis indicated these variation sites were pathogenic and resulted in abnormal three-dimensional protein structures, likely being the main cause of Nance-Horan syndrome. Conclusion: The majority of patients from the three Nance-Horan syndrome families studied were affected by congenital hereditary cataracts characterized by nuclear opacities.The NHS gene variations c.2519_2520del, exon3del, and c.3847C>T are newly identified pathogenic sites in Nance-Horan syndrome, reported for the first time across three different families.
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Catarata , Mutación , Linaje , Humanos , Masculino , Femenino , Catarata/genética , Catarata/congénito , Adulto , Persona de Mediana Edad , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Fenotipo , Pueblo Asiatico/genética , Anomalías Dentarias/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Enfermedades Hereditarias del Ojo/genética , Niño , China , Proteínas de la MembranaRESUMEN
OsS1Fa1, a homologue of spinach S1Fa, is a small protein in rice that contains four distinct conserved motifs and participates in drought tolerance. However, the biological functions of these conserved motifs have not been characterized to date. Therefore, we investigated the roles of these conserved domains in the localization and cellular function of OsS1Fa1. We analysed the subcellular localization of OsS1Fa1 using confocal laser scanning microscopy (CLSM), following particle bombardment and bacterial infiltration. An E. coli in vivo reconstituted sumoylation assay was conducted to investigate sumoylation of OsS1Fa1. We characterized the function of the transmembrane domain of OsS1Fa1 in drought tolerance using transgenic Arabidopsis plants. Fluorescence analysis showed that OsS1Fa1 localized to the nuclear and cytoplasmic membranes. Mutation and cell fractionation analyses revealed that the membrane localization domain determined the subcellular localization of OsS1Fa1. The rice homologue OsS1Fa2 and Arabidopsis orthologs AtS1Fa1, AtS1Fa2, and AtS1Fa3 also exhibited similar localization patterns as OsS1Fa1. Sumoylation analysis demonstrated that OsS1Fa1 was conjugated with the small ubiquitin-related modifier (SUMO). Transgenic analysis showed that overexpression of OsS1Fa1(TMm1), a mutant form of the transmembrane domain of OsS1Fa1, in Arabidopsis did not enhance drought stress tolerance, whereas OsS1Fa1 overexpression improved the drought tolerance of transgenic Arabidopsis. Our data indicate that rice and Arabidopsis S1Fa1 proteins localize in the nuclear and cytoplasmic membranes, and that transmembrane domain determines subcellular localization and plays an important role in drought stress tolerance.
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Human respiratory syncytial virus (HRSV) can infect individuals of all ages, with children under five years old, the elderly, and immunocompromised persons as the main high-risk groups. Although older children and adults often exhibit mild or no symptoms, they may still be potential carriers of the virus. Therefore, employing efficient, accurate, and rapid detection methods to timely identify infection sources and quickly halt transmission is an important means to curb the potential spread of the epidemic. However, the clinical manifestations of HRSV infection are difficult to distinguish from acute respiratory infections caused by other respiratory viruses, and the identification relies on the results of pathogen testing. This article summarizes four commonly used detection methods for HRSV based on detection principles: antigen detection, nucleic acid testing, antibody detection, and virus isolation. The advantages, disadvantages, principles, and applicable scenarios of these four methods are summarized and compared. Furthermore, the research progress and prospects of HRSV detection methods are reviewed.
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Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Humanos , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Infecciones por Virus Sincitial Respiratorio/diagnósticoRESUMEN
The prevalence of tick-borne pathogens (TBP), Orientia tsutsugamushi, Rickettsia and Borrelia spp. in wild small animals, namely wild rodents, is now widely investigated. This study is to present the prevalence and distribution of O. tsutsugamushi, Rickettsia and Borrelia spp. in wild small animals and ticks collected from Gyeonggi and Gangwon provinces, Republic of Korea (ROK) in 2014. A total of 131 wild small animals, rodents and shrews, and 2,954 ticks were collected from Gyeonggi and Gangwon provinces from May to November 2014. The wild small animals (KR1-9) and ticks (K1-17) were grouped in accordance with capture dates and locations. Among the wild small animals, a total of 393 tissues and blood samples were extracted from six selected small animal series (KR1-3, KR6-8). Also, each date and location-grouped ticks were identified for its species and pooled according to the stage of development. Molecular identification for Rickettsia, Orientia, and Borrelia species was performed using polymerase chain reaction (PCR). To detect TBPs among wild small animals and ticks, primer sets targeting the 56 kDa protein encoding gene of Orientia spp., outer membrane protein B gene (OmpB) of Rickettsia spp., and 5S-23S intergenic spacer region (IGS) gene of Borrelia spp. were used. Of the 393 wild small animals' blood and tissue samples, 199 (50.6%) were positive for Orientia spp., 158 (40.2%) were positive for Borrelia spp., and 55 (14.0%) were positive for Rickettsia spp. Moreover, a total of 14 tick pools (n = 377) was positive for Rickettsia spp. (n=128, 34.0%) and Borrelia spp. (n=33, 8.8%). High prevalence of Orientia spp. and Rickettsia spp. in rodents and shrews were observed. This study presents significant insights by presenting data collected in 2014 that the prevalence of TBP was already high in mid 2010s. This study highlights the sustainable routine surveillance model for TBP.
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Borrelia , Orientia tsutsugamushi , Rickettsia , Roedores , Musarañas , Garrapatas , Animales , Musarañas/parasitología , Musarañas/microbiología , Roedores/microbiología , Roedores/parasitología , Rickettsia/aislamiento & purificación , Rickettsia/genética , República de Corea/epidemiología , Orientia tsutsugamushi/genética , Orientia tsutsugamushi/aislamiento & purificación , Borrelia/aislamiento & purificación , Borrelia/genética , Garrapatas/microbiología , Enfermedades por Picaduras de Garrapatas/epidemiología , Enfermedades por Picaduras de Garrapatas/microbiología , Enfermedades por Picaduras de Garrapatas/veterinaria , Reacción en Cadena de la Polimerasa , Animales Salvajes/microbiología , Animales Salvajes/parasitología , Tifus por Ácaros/epidemiología , Tifus por Ácaros/veterinaria , Tifus por Ácaros/microbiologíaRESUMEN
Objective: To investigate the prevalence of diabetes in the elderly aged ≥60 years in Liaoning Province from 2017 to 2019 and analyze the impact of blood glucose control on all-cause mortality and cardiovascular disease (CVD) mortality. Methods: A survey was conducted in the elderly aged ≥60 years in Liaoning from 2017 to 2019 to collect the information about the prevalence of diabetes and other chronic diseases in the diabetes patients. The mortality of the enrolled subjects was investigated in September 2023. Cox proportional hazards regression models were used to estimate the association between blood glucose control in the elderly with diabetes and the risks of all-cause mortality and CVD mortality. Results: The crude prevalence of diabetes in the elderly aged ≥60 years was 20.2% (2 014/9 958) in Liaoning from 2017 to 2019, and the standardized prevalence rate was 19.9%. The prevalence rates of hypertension, dyslipidemia, and overweight/obesity in the diabetes patients were 77.0%, 51.7%, and 67.5% respectively. The median follow-up time was 5.5 years, and the all-cause mortality and CVD mortality rates in the diabetes patients were 244.3/10 000 person-years and 142.9/10 000 person-years, respectively. The results of the Cox proportional hazards regression model analysis showed that compared with non-diabetic individuals, diabetes patients had an increased risk of all-cause mortality by 1.68 times [hazard ratio (HR)=1.68, 95%CI: 1.44-1.94] and an increased risk of CVD mortality by 1.56 times (HR=1.56, 95%CI: 1.29-1.89). The differences in risks of all-cause mortality and CVD mortality between the diabetes patients with normal fasting blood glucose and glycated hemoglobin levels and people without diabetes were not significant (all P>0.05). The failure to meet either the FPG or HbA1c target increased the risk of all-cause mortality (all P<0.05). For individuals who failed to meet the HbA1c target, there was an increased risk of CVD mortality (all P<0.05). Conclusions: The comorbidity rate of chronic diseases was higher in the elderly with diabetes than in the elderly without diabetes in Liaoning. Elderly diabetes patients can benefit from good blood glucose control.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Modelos de Riesgos Proporcionales , Humanos , Anciano , Prevalencia , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus/epidemiología , Persona de Mediana Edad , China/epidemiología , Masculino , Femenino , Factores de Riesgo , Glucemia/análisis , Hipertensión/epidemiología , Anciano de 80 o más Años , Dislipidemias/epidemiología , Obesidad/epidemiología , Obesidad/complicacionesRESUMEN
BACKGROUND: This study aimed to clarify the efficacy and safety of minimally invasive transabdominal surgery (MIS) with transperineal minimal invasive surgery (tpMIS) for sacrectomy in advanced primary and recurrent pelvic malignancies. METHODS: Using a prospectively collected database, we retrospectively analyzed the clinical, surgical, and pathological outcomes of MIS with tpMIS for sacrectomies. Surgery was performed between February 2019 and May 2023. The median follow-up period was 27 months (5-46 months). RESULTS: Fifteen consecutive patients were included in this analysis. The diagnoses were as follows: recurrent rectal cancer, n = 11 (73%); primary rectal cancer, n = 3 (20%); and recurrent ovarian cancer, n = 1 (7%). Seven patients (47%) underwent pelvic exenteration with sacrectomy, six patients (40%) underwent abdominoperineal resection (APR) with sacrectomy, and two patients (13%) underwent tumor resection with sacrectomy. The median intraoperative blood loss was 235 ml (range 45-1320 ml). The postoperative complications (Clavien-Dindo grade ≥ 3a) were graded as follows: 3a, n = 6 (40%); 3b, n = 1 (7%); and ≥ 4, n = 0 (0%). Pathological examinations demonstrated that R0 was achieved in 13 patients (87%). During the follow-up period, two patients (13%) developed local re-recurrence due to recurrent cancer. The remaining 13 patients (87%) had no local disease. Fourteen patients (93%) survived. CONCLUSIONS: Although the patient cohort in this study is heterogeneous, MIS with tpMIS was associated with a very small amount of blood loss, a low incidence of severe postoperative complications, and an acceptable R0 resection rate. Further studies are needed to clarify the long-term oncological feasibility.
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Estudios de Factibilidad , Procedimientos Quirúrgicos Mínimamente Invasivos , Recurrencia Local de Neoplasia , Perineo , Humanos , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Masculino , Perineo/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Adulto , Resultado del Tratamiento , Neoplasias Pélvicas/cirugía , Sacro/cirugía , Exenteración Pélvica/métodos , Exenteración Pélvica/efectos adversos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patologíaRESUMEN
1. The production of goose eggs holds significant economic value on a global scale and the quality of fertilised eggs is crucial for the successful hatching and sustained development of the poultry industry. Developing a low-cost fertilised egg identification system that is suitable for large-scale testing is of great significance. However, existing methods are expensive and have high environmental detection requirements, which limit their promotion.2. To address this issue, an improved object detection model called FEDM based on YOLOv5 is proposed, which has been shown to be outstanding among nine models. The main network of YOLOv5 is enhanced with the SENet attention mechanism to improve the feature selection capability. The C3_DCNv3 is introduced to enhance the detection ability of blood vessels in the fertilised eggs. The application of Dyhead significantly improved the representation capacity of the object detection head without any computational overhead. The loss function is replaced with MPDIoU to simplify the calculation process.3. Experimental results from the augmented dataset showed that the average precision of the FEDM reached 96.7%, which is a 5.5% improvement compared to the YOLOv5s model. FEDM exhibited better detection performance on eggs from different shooting angles than the YOLOv5 algorithm and achieves high detection speed.4. The FEDM secured significant advancement on the detection rate of the fourth day fertilised egg compared to the YOLOv5 algorithm. Based on this result, savings and space utilisation can be made, which has practical application value.
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OBJECTIVE: The primary surgical techniques used to treat localized renal tumors are laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN). Obese patients have more intra-abdominal fat accumulation, which may make the localization and operation in minimally invasive surgery more complicated. Currently, limited research has been conducted on which method is more suitable for performing a partial nephrectomy on obese individuals. The aim of our investigation was to analyze and compare the perioperative results associated with both approaches to offer valuable information about the selection of LPN or RAPN as an optimal choice when performing a partial nephrectomy in obese patients. PATIENTS AND METHODS: We retrospectively collected clinical data from 78 cases of obese individuals [Body mass index (BMI) > 28] who underwent RAPN, as well as 50 cases of obese individuals (BMI > 28) who underwent LPN. The analysis covered various aspects, including initial patient characteristics, glomerular filtration rate (GFR), warm ischemia time (WIT), operation time, volume of blood loss during the surgical procedure, time taken to recover bowel function, positive surgical margin rate, incidence of postoperative complications, and postoperative hospital stay. RESULTS: We observed that RAPNs exhibited shorter warm ischemia time and reduced intraoperative blood loss in obese patients, along with decreased postoperative duration of abdominal drainage and hospitalization periods compared to LPNs. CONCLUSIONS: In obese patients, RAPN demonstrates advantages over LPN in minimizing intraoperative blood loss, WIT, and facilitating postoperative recovery. These findings may serve as valuable evidence when considering the choice between LPN or RAPN for partial nephrectomy in obese individuals.
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Neoplasias Renales , Laparoscopía , Nefrectomía , Obesidad , Procedimientos Quirúrgicos Robotizados , Humanos , Nefrectomía/métodos , Nefrectomía/efectos adversos , Obesidad/cirugía , Obesidad/complicaciones , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Neoplasias Renales/cirugía , Resultado del Tratamiento , Anciano , Complicaciones Posoperatorias/epidemiología , Adulto , Tiempo de Internación , Tempo OperativoRESUMEN
Objective: This study aimed at investigating the efficacy and safety of eltrombopag in the treatment of adult primary immune thrombocytopenia (ITP) and evaluated the factors influencing its efficacy and side effects. Methods: A total of 198 patients with adult ITP who were admitted to Tianjin Medical University General Hospital between January 2018 and March 2022 were retrospectively analyzed. The efficacy of each starting dose of eltrombopag was evaluated, and adverse events were analyzed. The factors influencing efficacy were investigated, including sex, age, adult ITP type, platelet antibodies, and combined drug treatments. Results: Of the 198 patients, 70 males and 128 females with a median age of 45 years (18-88 years) were included; 130 (65.7%) had newly diagnosed adult ITP, 25 (12.6%) had persistent adult ITP, and 43 (21.7%) had chronic adult ITP. The bleeding event scores at baseline were assessed; 84.3% had scores of<4 and 15.7% had scores of ≥4. The eltrombopag response rate (initial response) at 6 weeks was 78.8% (complete response [CR]: 49.0%; CR1: 14.6%; CR2: 15.2%). The median response time to eltrombopag was 7 (7, 14) days. The initial response rates to 25, 50, and 75 mg eltrombopag were 74.1%, 85.9%, and 60.0%, respectively (P=0.031). The initial response rate to the 50 mg dose was significantly higher than that of the 25-mg and 75-mg doses. Two patients received 100 mg as the starting dose, and their initial response was 0. Regarding dose adjustment, 70.7% of the patients remained on the starting dose, 8.6% underwent dose adjustment to 50 mg, and 6.1% underwent dose adjustment to 75 mg. Another two patients underwent dose adjustment to 100 mg. After dose adjustment, the persistent response rates were 83.6%, 85.3%, and 85.7% for the 25-, 50-, and 75-mg doses, respectively, with no significant difference. After dose adjustment, the sustained efficacy rate for the 100-mg dose (4 patients) was 100.0%. After 6 weeks of treatment with eltrombopag, the overall bleeding score of patients with ITP decreased. The number of patients with a score of ≥4 decreased to 0, the number of patients with a score of<4 decreased, and there was no significant change in the number of patients with a score of 1-2. The most common adverse event associated with eltrombopag was impaired liver function (7.7%). No thrombosis events or other adverse events were observed. ITP type and number of megakaryocytes significantly affected the initial response to eltrombopag. The initial response rates to eltrombopag for newly diagnosed adult ITP, persistent adult ITP, and chronic adult ITP were 85.3%, 56.0%, and 76.2%, respectively (P=0.003). For megakaryocytes, the initial response rates were 61.8%, 87.1%, and 84.3% (P=0.009) for the decreased, normal, and increased megakaryocyte groups, respectively. Conclusion: Eltrombopag, as a second-line or higher treatment for adult ITP, has a rapid onset of action and good safety. The initial response rate is significantly higher with a dose of 50 mg than with a dose of 25 mg. Patients with newly diagnosed ITP and those with normal or increased megakaryocyte numbers have a higher initial response rate to eltrombopag.
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Benzoatos , Hidrazinas , Púrpura Trombocitopénica Idiopática , Pirazoles , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Adulto , Anciano , Pirazoles/administración & dosificación , Pirazoles/uso terapéutico , Benzoatos/administración & dosificación , Benzoatos/uso terapéutico , Benzoatos/efectos adversos , Hidrazinas/uso terapéutico , Hidrazinas/administración & dosificación , Adolescente , Anciano de 80 o más Años , Resultado del Tratamiento , Niño , Adulto Joven , HemorragiaRESUMEN
ADHD is a common chronic neurodevelopmental disorder and is characterized by persistent inattention, hyperactivity, impulsivity and are often accompanied by learning and memory impairment. Great evidence has shown that learning and memory impairment of ADHD plays an important role in its executive function deficits, which seriously affects the development of academic, cognitive and daily social skills and will cause a serious burden on families and society. With the increasing attention paid to learning and memory impairment in ADHD, relevant research is gradually increasing. In this article, we will present the current research results of learning and memory impairment in ADHD from the following aspects. Firstly, the animal models of ADHD, which display the core symptoms of ADHD as well as with learning and memory impairment. Secondly, the molecular mechanism of has explored, including some neurotransmitters, receptors, RNAs, etc. Thirdly, the susceptibility gene of ADHD related to the learning and impairment in order to have a more comprehensive understanding of the pathogenesis. Key words: Learning and memory, ADHD, Review.
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Trastorno por Déficit de Atención con Hiperactividad , Trastornos de la Memoria , Trastorno por Déficit de Atención con Hiperactividad/psicología , Trastorno por Déficit de Atención con Hiperactividad/genética , Humanos , Animales , Trastornos de la Memoria/psicología , Trastornos de la Memoria/etiología , Aprendizaje , Modelos Animales de Enfermedad , Discapacidades para el Aprendizaje/psicología , Discapacidades para el Aprendizaje/etiología , MemoriaRESUMEN
Objective: To explore the antiviral activity of the small-molecule compound AM679 in hepatitis B virus (HBV) replication and infection cell models. Methods: The positive regulatory effect of AM679 on EFTUD2 expression was validated by qPCR and Western blotting. HepAD38 and HepG2-NTCP cells were treated with AM679 (0.5, 1, and 2 nmol/L). Negative control, positive control, and AM679 combined with the entecavir group were set up. HBV DNA intra-and extracellularly, as well as the expression levels of intracellular HBV total RNAs and 3.5kb-RNA changes, were detected with qPCR. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels were measured in the cell supernatant by an enzyme-linked immunosorbent assay (ELISA). The t-test method was used for the statistical analysis of the mean difference between groups. Results: EFTUD2 mRNA and protein expression levels were significantly increased in HepAD38 and HepG2-NTCP cells following AM679 treatment, with a statistically significant difference (Pâ <â 0.001). Intra-and extracellular indicators such as HBV DNA, HBV RNAs, HBV 3.5kb-RNA, HBsAg, and HBeAg were decreased to varying degrees in both cell models, and the decrease in these indicators was more pronounced with the increase in AM679 concentration and prolonged treatment duration, while the combined use of AM679 and entecavir had a more significant antiviral effect. The HBV DNA inhibition rates in the supernatant of HepAD38 cells with the use of 2 nmol/L AM679 were 21% and 48% on days three and nine, respectively. The AM679 combined with the ETV treatment group had the most significant inhibitory effect (62%), with a Pâ <â 0.01. More active HBV replication was observed after silencing EFTUD2, while the antiviral activity of AM679 was significantly weakened. Conclusion: AM679 exerts anti-HBV activity in vitro by targeting the regulation of EFTUD2 expression.
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Antivirales , Virus de la Hepatitis B , Replicación Viral , Humanos , Antivirales/farmacología , ADN Viral , Guanina/análogos & derivados , Células Hep G2 , Antígenos e de la Hepatitis B/metabolismo , Antígenos de Superficie de la Hepatitis B/metabolismo , Virus de la Hepatitis B/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Indoles/química , Indoles/farmacología , Ácidos Pentanoicos/química , Ácidos Pentanoicos/farmacología , Factores de Elongación de Péptidos/antagonistas & inhibidores , Factores de Elongación de Péptidos/metabolismo , Ribonucleoproteína Nuclear Pequeña U5/antagonistas & inhibidores , Ribonucleoproteína Nuclear Pequeña U5/metabolismoRESUMEN
Tracking pathogen transmissibility during infectious disease outbreaks is essential for assessing the effectiveness of public health measures and planning future control strategies. A key measure of transmissibility is the time-dependent reproduction number, which has been estimated in real-time during outbreaks of a range of pathogens from disease incidence time series data. While commonly used approaches for estimating the time-dependent reproduction number can be reliable when disease incidence is recorded frequently, such incidence data are often aggregated temporally (for example, numbers of cases may be reported weekly rather than daily). As we show, commonly used methods for estimating transmissibility can be unreliable when the timescale of transmission is shorter than the timescale of data recording. To address this, here we develop a simulation-based approach involving Approximate Bayesian Computation for estimating the time-dependent reproduction number from temporally aggregated disease incidence time series data. We first use a simulated dataset representative of a situation in which daily disease incidence data are unavailable and only weekly summary values are reported, demonstrating that our method provides accurate estimates of the time-dependent reproduction number under such circumstances. We then apply our method to two outbreak datasets consisting of weekly influenza case numbers in 2019-20 and 2022-23 in Wales (in the United Kingdom). Our simple-to-use approach will allow accurate estimates of time-dependent reproduction numbers to be obtained from temporally aggregated data during future infectious disease outbreaks.
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Número Básico de Reproducción , Teorema de Bayes , Brotes de Enfermedades , Gripe Humana , Humanos , Incidencia , Gripe Humana/epidemiología , Gripe Humana/transmisión , Brotes de Enfermedades/estadística & datos numéricos , Número Básico de Reproducción/estadística & datos numéricos , Factores de Tiempo , Simulación por Computador , Gales/epidemiología , Modelos EpidemiológicosRESUMEN
Objective: To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies. Methods: This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months. Results: Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work. Conclusions: Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.
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Errores Innatos del Metabolismo de los Aminoácidos , Mutación , Humanos , Masculino , Femenino , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/genética , Adolescente , Estudios Retrospectivos , Niño , Estudios de Seguimiento , Edad de Inicio , Fenotipo , Genotipo , Pronóstico , Ácido Metilmalónico/sangre , Vitamina B 12 , OxidorreductasasRESUMEN
Objective: To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) . Methods: A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period. Results: Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site. Conclusion: The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.
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Anemia Ferropénica , Disacáridos , Humanos , Sacarato de Óxido Férrico/uso terapéutico , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/inducido químicamente , Infusiones Intravenosas , Estudios Retrospectivos , Compuestos Férricos/uso terapéutico , Compuestos Férricos/efectos adversos , Hierro , Hemoglobinas/análisis , Hemoglobinas/uso terapéuticoRESUMEN
Periodontal tissue destruction in periodontitis is a consequence of the host inflammatory response to periodontal pathogens, which could be aggravated in the presence of type 2 diabetes mellitus (T2DM). Accumulating evidence highlights the intricate involvement of macrophage-mediated inflammation in the pathogenesis of periodontitis under both normal and T2DM conditions. However, the underlying mechanism remains elusive. Alpha-2-glycoprotein 1 (AZGP1), a glycoprotein featuring an MHC-I domain, has been implicated in both inflammation and metabolic disorders. In this study, we found that AZGP1 was primarily colocalized with macrophages in periodontitis tissues. AZGP1 was increased in periodontitis compared with controls, which was further elevated when accompanied by T2DM. Adeno-associated virus-mediated overexpression of Azgp1 in the periodontium significantly enhanced periodontal inflammation and alveolar bone loss, accompanied by elevated M1 macrophages and pyroptosis in murine models of periodontitis and T2DM-associated periodontitis, while Azgp1-/- mice exhibited opposite effects. In primary bone marrow-derived macrophages stimulated by lipopolysaccharide (LPS) or LPS and palmitic acid (PA), overexpression or knockout of Azgp1 markedly upregulated or suppressed, respectively, the expression of macrophage M1 markers and key components of the NLR Family Pyrin Domain Containing 3 (NLRP3)/caspase-1 signaling. Moreover, conditioned medium from Azgp1-overexpressed macrophages under LPS or LPS+PA stimulation induced higher inflammatory activation and lower osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs). Furthermore, elevated M1 polarization and pyroptosis in macrophages and associated detrimental effects on hPDLSCs induced by Azgp1 overexpression could be rescued by NLRP3 or caspase-1 inhibition. Collectively, our study elucidated that AZGP1 could aggravate periodontitis by promoting macrophage M1 polarization and pyroptosis through the NLRP3/casapse-1 pathway, which was accentuated in T2DM-associated periodontitis. This finding deepens the understanding of AZGP1 in the pathogenesis of periodontitis and suggests AZGP1 as a crucial link mediating the adverse effects of diabetes on periodontal inflammation.
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Diabetes Mellitus Tipo 2 , Macrófagos , Periodontitis , Piroptosis , Zn-alfa-2-Glicoproteína , Animales , Humanos , Masculino , Ratones , Pérdida de Hueso Alveolar/metabolismo , Caspasa 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animales de Enfermedad , Glicoproteínas/metabolismo , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Periodontitis/metabolismo , Periodontitis/inmunología , Transducción de Señal , Zn-alfa-2-Glicoproteína/genética , Zn-alfa-2-Glicoproteína/metabolismoRESUMEN
Objective: To explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency. Methods: This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively. Results: The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 µmol/L) was found in all patients, and decreased to 20-70 µmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders. Conclusions: Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.
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Metilenotetrahidrofolato Reductasa (NADPH2) , Espasticidad Muscular , Adolescente , Niño , Femenino , Humanos , Masculino , Homocisteína/uso terapéutico , Homocistinuria , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/deficiencia , Espasticidad Muscular/diagnóstico , Espasticidad Muscular/genética , Espasticidad Muscular/tratamiento farmacológico , Trastornos Psicóticos , Estudios RetrospectivosRESUMEN
Objective: To evaluate the diagnostic value of gene testing in familial hypercholesterolemia (FH) in patients with premature myocardial infarction(PMI). Methods: This study was a single center cross-sectional study. A retrospective analysis was made on PMI patients who visited the People's Hospital of Peking University from May 1, 2015 to March 31, 2017. Clinical data of patients was collected and gene testing of FH related genes low density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B(APOB) and low density lipoprotein receptor adaptor protein 1(LDLRAP1) was carried out. Clinical diagnosis of FH patients was performed using Simon Broome criteria, DLCN criteria, and FH Chinese expert consensus. Results: There were 188 males (83.6%) among 225 PMI patients, and the age of the first myocardial infarction was (46.6±7.2) years old. Ten patients carried FH pathogenic or possibly pathogenic mutations (4.4%). Compared with Simon Broome standard, DLCN standard and FH Chinese expert consensus, gene testing increased the diagnostic rate of FH by 53.3%, 33.3% and 42.1% respectively. Conclusion: Gene testing is helpful to improve the diagnosis of FH, and it is important to start the standard treatment of FH as early as possible in patients with premature myocardial infarction.