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1.
Vaccines (Basel) ; 12(9)2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39340103

RESUMEN

BACKGROUND: In 2020, the WHO proposed the global strategic goal of accelerating the elimination of cervical cancer (CC). One of the key strategies is that, by 2030, 90% of girls will complete HPV vaccination by age 15. In 2017, HPV vaccines were first marketed in China. OBJECTIVES: This study aimed to explore the changes in parents' knowledge about CC, HPV, HPV vaccines, and acceptance of HPV vaccination 5 years after the introduction of HPV vaccines into China. Associated factors and reasons for refusal by parents were also explored. METHODS: A school-based follow-up study was conducted among parents in China from May 2018 to May 2023. Comparison using Chi-square tests was performed to measure the changes. Univariate and multivariate analyses were used to explore factors associated with HPV vaccination among teenage girls. RESULTS: The overall cognitive level in terms of CC- and HPV-related knowledge among parents increased, and they expressed more willingness to vaccinate their daughter (35.4% in 2018 vs. 56.6% in 2023). The HPV vaccination rate among teenage girls remained at a low level (4.4% in 2018, 9.8% in 2023). The main obstacles reported by parents were limited knowledge (42.0%), scarcity of the HPV vaccine (29.2%), waiting until their daughter was older (27.5%), safety concerns (14.7%), high cost (9.0%), and effectiveness concerns (4.6%). Parents who are elderly, local residents, have received HPV vaccines themselves, have had experience of vaccinating their children with influenza vaccines, and have a higher knowledge level of CC, HPV and HPV vaccines are more likely to vaccinate their children with HPV vaccines. CONCLUSIONS: Although we observed an increment in parents' knowledge level in terms of CC, HPV, HPV vaccines, and HPV vaccine uptake over the past 5 years, the HPV vaccine coverage among girls still falls short of the WHO's 2030 target. Comprehensive intervention strategies, including tailored health education among adolescents and their parents, doctor recommendations, and providing financial subsidies or free HPV vaccines are needed in China.

2.
Int J Biol Macromol ; 278(Pt 2): 134416, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39098700

RESUMEN

Inbreeding can lead to the accumulation of homozygous single nucleotide polymorphisms (SNPs) in the genome, which can significantly affect gene expression and phenotype. In this study, we examined the impact of homozygous SNPs resulting from inbreeding on alternative polyadenylation (APA) site selection and the underlying genetic mechanisms using inbred Luchuan pigs. Genome resequencing revealed that inbreeding results in a high accumulation of homozygous SNPs within the pig genome. 3' mRNA-seq on leg muscle, submandibular lymph node, and liver tissues was performed to identify differences in APA events between inbred and outbred Luchuan pigs. We revealed different tissue-specific APA usage caused by inbreeding, which were associated with different biological processes. Furthermore, we explored the role of polyadenylation signal (PAS) SNPs in APA regulation under inbreeding and identified key genes such as PUM1, SCARF1, RIPOR2, C1D, and LRRK2 that are involved in biological processes regulation. This study provides resources and sheds light on the impact of genomic homozygosity on APA regulation, offering insights into genetic characteristics and biological processes associated with inbreeding.


Asunto(s)
Endogamia , Poliadenilación , Polimorfismo de Nucleótido Simple , Animales , Poliadenilación/genética , Porcinos/genética , Genoma , Homocigoto , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especificidad de Órganos/genética
3.
JMIR Public Health Surveill ; 10: e52666, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39213137

RESUMEN

Background: Infectious disease-specific health literacy (IDSHL) is a crucial factor in the development of infectious diseases. It plays a significant role not only in mitigating the resurgence of infectious diseases but also in effectively averting the emergence of novel infections such as COVID-19. During the 3 years of the COVID-19 pandemic, China primarily adopted nonpharmaceutical interventions, advocating for people to avoid crowded places and wear masks to prevent the spread of COVID-19. Consequently, there has been a dearth of research concerning IDSHL and its corresponding focal points for health education. Objective: This study aimed to (1) evaluate the changes in IDSHL scores between 2019 (before the COVID-19 pandemic) and 2022 (the postepidemic period of COVID-19) and (2) explore the risk factors affecting IDSHL using a multivariate logistic regression analysis. Methods: This study used 2-round cross-sectional surveys, conducted in 2019 and 2022, respectively, in 30 counties in Zhejiang Province, China. Multiple-stage stratified random sampling was used to select households, and a Kish grid was used to identify participants. An identical standardized questionnaire consisting of 12 closed-ended questions was used to measure IDSHL scores before and after the COVID-19 pandemic (2019 and 2022). Standard descriptive statistics, chi-square tests, t tests, and multivariate logistic regression analyses were used to analyze the data. Results: The 2-round cross-sectional surveys conducted in 2019 and 2022 yielded, out of 19,366 and 19,221 total questionnaires, 19,257 (99.44% response rate) and 18,857 (98.11% response rate) valid questionnaires, respectively. The correct response rate for the respiratory infectious diseases question "When coughing or sneezing, which of the following is correct?" increased from 29.10% in 2019 to 37.92% in 2022 (χ²1=332.625; P<.001). The correct response rate for the nonrespiratory infectious diseases question "In which of the following ways can hepatitis B be transmitted to others?" decreased from 64.28% to 59.67% (χ²1=86.059; P<.001). In terms of IDSHL scores, a comparison between 2022 and 2019 revealed notable statistical differences in the overall scores (t1=10.829; P<.001) and across the 3 dimensions of knowledge (t1=8.840; P<.001), behavior (t1=16.170; P<.001), and skills (t1=9.115; P<.001). With regard to the questions, all but 4 exhibited statistical differences (P<.001). Multivariate logistic regression analyses indicated that the 2022 year group had a higher likelihood of possessing acquired IDSHL than the 2019 group (odds ratio 1.323, 95% CI 1.264-1.385; P<.001). Conclusions: When conducting health education, it is imperative to enhance efforts in nonrespiratory infectious disease health education, as well as respiratory infectious diseases such as COVID-19. Health education interventions should prioritize ethnic minority populations with a poor self-health status and low education.


Asunto(s)
COVID-19 , Alfabetización en Salud , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Transversales , Alfabetización en Salud/estadística & datos numéricos , China/epidemiología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Encuestas y Cuestionarios , Pandemias , Enfermedades Transmisibles/epidemiología , Adulto Joven , Adolescente
4.
Signal Transduct Target Ther ; 9(1): 216, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39143065

RESUMEN

Third-generation EGFR tyrosine kinase inhibitors (TKIs), exemplified by osimertinib, have demonstrated promising clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). Our previous work has identified ASK120067 as a novel third-generation EGFR TKI with remarkable antitumor effects that has undergone New Drug Application (NDA) submission in China. Despite substantial progress, acquired resistance to EGFR-TKIs remains a significant challenge, impeding the long-term effectiveness of therapeutic approaches. In this study, we conducted a comprehensive investigation utilizing high-throughput proteomics analysis on established TKI-resistant tumor models, and found a notable upregulation of branched-chain amino acid transaminase 1 (BCAT1) expression in both osimertinib- and ASK120067-resistant tumors compared with the parental TKI-sensitive NSCLC tumors. Genetic depletion or pharmacological inhibition of BCAT1 impaired the growth of resistant cells and partially re-sensitized tumor cells to EGFR TKIs. Mechanistically, upregulated BCAT1 in resistant cells reprogrammed branched-chain amino acid (BCAA) metabolism and promoted alpha ketoglutarate (α-KG)-dependent demethylation of lysine 27 on histone H3 (H3K27) and subsequent transcriptional derepression of glycolysis-related genes, thereby enhancing glycolysis and promoting tumor progression. Moreover, we identified WQQ-345 as a novel BCAT1 inhibitor exhibiting antitumor activity both in vitro and in vivo against TKI-resistant lung cancer with high BCAT1 expression. In summary, our study highlighted the crucial role of BCAT1 in mediating resistance to third-generation EGFR-TKIs through epigenetic activation of glycolysis in NSCLC, thereby supporting BCAT1 as a promising therapeutic target for the treatment of TKI-resistant NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Resistencia a Antineoplásicos , Epigénesis Genética , Receptores ErbB , Glucólisis , Neoplasias Pulmonares , Inhibidores de Proteínas Quinasas , Transaminasas , Humanos , Receptores ErbB/genética , Receptores ErbB/metabolismo , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Transaminasas/genética , Transaminasas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Glucólisis/efectos de los fármacos , Glucólisis/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Epigénesis Genética/efectos de los fármacos , Epigénesis Genética/genética , Ratones , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Acrilamidas/farmacología , Animales , Compuestos de Anilina/farmacología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Indoles , Pirimidinas
5.
China CDC Wkly ; 6(31): 767-771, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39118872

RESUMEN

What is already known on this topic?: A new conceptual term, small and vulnerable newborns (SVN), bringing preterm birth, small for gestational age (SGA), or low birth weight (LBW) together is being advocated for assessing whether a child is at high risk. What is added by this report?: According to the new conceptual term, the increasing incidence of high-risk newborns (from 9.82% to 10.96%) has been observed among 2,005,408 newborns over the period from 2013 to 2022, which is higher than using any of the three definitions of SVN. Maternal age ≥35, primiparity, and multiple births are high risks for SVN. What are the implications for public health practice?: The new conceptual framework should be used to better assess the number of high-risk newborns. Attention should be paid to multiple births to prevent preterm-related SVN. To reduce term newborns who are SGA, we need to be concerned not only with multiple pregnancies but also with first-time mothers.

6.
China CDC Wkly ; 6(31): 786-792, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39118870

RESUMEN

What is already known about this topic?: With socioeconomic development, the increase of older pregnancies and multiparas has brought risks to mothers and infants. What is added by this report?: As parities increased, the proportion of women of advanced maternal age (AMA) and non-local domicile increased, while the proportion of women with higher education levels decreased. Women with ≥3 parities are more likely to have preterm birth (PTB) and macrosomia. What are the implications for public health practice?: A comprehensive analysis of pregnancy traits among women at different parities offers a robust foundation for tailored strategies against adverse pregnancy outcomes.

7.
Commun Biol ; 7(1): 972, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39122786

RESUMEN

Dental pulp stem cells (DPSC) have shown osteogenic and bone regenerative potential. Improving the in situ bone regeneration potential of DPSC is crucial for their application as seed cells during bone defect reconstruction in clinics. This study aimed to develop DPSC-derived organoid-like microspheroids as effective seeds for bone tissue engineering applications. DPSC osteogenic microspheroids (70 µm diameter) were cultured in a polydimethylsiloxane-mold-based agarose-gel microwell-culture-system with or without cannabidiol (CBD)-treatment. Results of in vitro studies showed higher osteogenic differentiation potential of microspheroids compared with 2D-cultured-DPSC. CBD treatment further improved the osteogenic differentiation potential of microspheroids. The effect of CBD treatment in the osteogenic differentiation of microspheroids was more pronounced compared with that of CBD-treated 2D-cultured-DPSC. Microspheroids showed a higher degree of bone regeneration in nude mice calvarial bone defect compared to 2D-cultured-DPSC. CBD-treated microspheroids showed the most robust in situ bone regenerative potential compared with microspheroids or CBD-treated 2D-cultured-DPSC. According to mRNA sequencing, bioinformatic analysis, and confirmation study, the higher osteogenic potential of CBD-treated microspheroids was mainly attributed to WNT6 upregulation. Taken together, DPSC microspheroids have robust osteogenic potential and can effectively translate the effect of in vitro osteoinductive stimulation during in situ bone regeneration, indicating their application potential during bone defect reconstruction in clinics.


Asunto(s)
Cannabidiol , Diferenciación Celular , Pulpa Dental , Osteogénesis , Células Madre , Regulación hacia Arriba , Osteogénesis/efectos de los fármacos , Animales , Cannabidiol/farmacología , Células Madre/efectos de los fármacos , Células Madre/metabolismo , Células Madre/citología , Ratones , Regulación hacia Arriba/efectos de los fármacos , Pulpa Dental/citología , Pulpa Dental/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Organoides/efectos de los fármacos , Organoides/metabolismo , Humanos , Ratones Desnudos , Células Cultivadas , Regeneración Ósea/efectos de los fármacos
8.
J Integr Plant Biol ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023402

RESUMEN

Although green light (GL) is located in the middle of the visible light spectrum and regulates a series of plant developmental processes, the mechanism by which it regulates seedling development is largely unknown. In this study, we demonstrated that GL promotes atypical photomorphogenesis in Arabidopsis thaliana via the dual regulations of phytochrome B (phyB) and phyA. Although the Pr-to-Pfr conversion rates of phyB and phyA under GL were lower than those under red light (RL) in a fluence rate-dependent and time-dependent manner, long-term treatment with GL induced high Pfr/Pr ratios of phyB and phyA. Moreover, GL induced the formation of numerous small phyB photobodies in the nucleus, resulting in atypical photomorphogenesis, with smaller cotyledon opening angles and longer hypocotyls in seedlings compared to RL. The abundance of phyA significantly decreased after short- and long-term GL treatments. We determined that four major PHYTOCHROME-INTERACTING FACTORs (PIFs: PIF1, PIF3, PIF4, and PIF5) act downstream of phyB in GL-mediated cotyledon opening. In addition, GL plays opposite roles in regulating different PIFs. For example, under continuous GL, the protein levels of all PIFs decreased, whereas the transcript levels of PIF4 and PIF5 strongly increased compared with dark treatment. Taken together, our work provides a detailed molecular framework for understanding the role of the antagonistic regulations of phyB and phyA in GL-mediated atypical photomorphogenesis.

9.
Nutrients ; 16(13)2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38999901

RESUMEN

BACKGROUND: Research on maternal weight gain in early pregnancy with healthy live offspring is lacking for Chinese women. Based on the China birth cohort study (CBCS), we aimed to explore maternal weight gain in different groups. METHODS: Singleton pregnancies of 6 + 0~13 + 6 weeks of gestation from the CBCS were considered, not including missing data or outliers, those lost at follow-up, or those with non-typical conditions of the offspring. Maternal first-trimester weight and body mass index (BMI) gain was considered as the early pregnancy weight minus the pre-pregnancy weight. Using Pearson's or Spearman's correlation and linear regression models to explore the relationship between maternal weight and BMI gain and gestational age (GA), stratified and sensitivity analyses were carried out to identify the study's robustness. RESULTS: There were 25,292 singleton pregnancies with healthy live offspring who were ultimately enrolled, and there was a linear correlation between GA and maternal weight gain (=0.55 + 0.05 × GA (weeks), p < 0.001, r2 = 0.002) and BMI change (=0.21 + 0.02 × GA (weeks), p < 0.001, r2 = 0.002). The association remained robust in the stratified and sensitivity analyses of the subgroups. CONCLUSIONS: Although the association between GA and maternal pre-pregnancy weight and BMI gain is weak, a slight correlation was shown, especially in pregnant women with a typical or low pre-pregnancy BMI, Han ethnicity, moderate levels of physical activity, natural conception, and folic acid (FA) and/or multivitamin supplementation.


Asunto(s)
Índice de Masa Corporal , Ganancia de Peso Gestacional , Humanos , Embarazo , Femenino , China , Adulto , Edad Gestacional , Cohorte de Nacimiento , Estudios de Cohortes , Primer Trimestre del Embarazo , Nacimiento Vivo , Aumento de Peso , Fenómenos Fisiologicos Nutricionales Maternos , Recién Nacido
10.
Clin Transl Sci ; 17(2): e13718, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39052984

RESUMEN

This study aimed to assess the safety, pharmacokinetics, and food impact on sudapyridine (WX-081), a novel drug designed to inhibit mycobacterium ATP synthase, with clinical applications for drug-resistant tuberculosis (TB) treatment. The research comprised two arms: a single ascending dose (SAD) arm (30 to 600 mg, N = 52) and a multiple ascending dose (MAD) arm (200 to 400 mg, N = 30). The influence of food was evaluated using a 400 mg dose within an SAD cohort. Plasma concentrations of WX-081 and M3 (main metabolite of WX-081) were analyzed using a validated liquid-chromatography tandem mass spectrometry method. In the SAD arm, mean residence time (MRT0-t), terminal half-life, and clearance of WX-081 ranged from 18.87 to 52.8 h, 31.39 to 236.57 h, and 6.4 to 80.34 L/h, respectively. The area under the curve from time zero to the last measurable timepoint (AUC0-t) of WX-081 showed dose-proportional increases in the SAD arm. The disparity between fasted and fed states of WX-081 was significant (p < 0.05), with fed dosing resulting in a 984.07% higher AUC0-t and 961.55% higher maximum plasma concentration. In both the SAD and MAD arms, one case each exhibited a 1 degree atrioventricular block. No QTc elongation was observed, and adverse events were not dose-dependent. Favorable exposure, tolerability, safety, and an extended MRT0-t suggest that WX-081 holds promise as a phase II development candidate for drug-resistant TB treatment.


Asunto(s)
Antituberculosos , Interacciones Alimento-Droga , Voluntarios Sanos , Humanos , Adulto , Masculino , Antituberculosos/farmacocinética , Antituberculosos/administración & dosificación , Antituberculosos/efectos adversos , Antituberculosos/sangre , Adulto Joven , Femenino , Relación Dosis-Respuesta a Droga , Persona de Mediana Edad , Área Bajo la Curva , Semivida , China , Pueblo Asiatico , Estudios Cruzados , Pueblos del Este de Asia
11.
Front Microbiol ; 15: 1419499, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38989028

RESUMEN

Rapid evolution of porcine reproductive and respiratory syndrome virus (PRRSV) is the bottleneck for effective prevention and control of PRRS. Thus, understanding the prevalence and genetic background of PRRSV strains in swine-producing regions is important for disease prevention and control. However, there is only limited information about the epizootiological situation of PRRS in the Xinjiang Uygur Autonomous Region, China. In this study, blood or lung tissue samples were collected from 1,411 PRRS-suspected weaned pigs from 9 pig farms in Changji, Shihezi, and Wujiaqu cities between 2020 and 2022. The samples were first tested by RT-quantitative PCR, yielding a PRRSV-2 positive rate of 53.6%. Subsequently, 36 PRRSV strains were isolated through initial adaptation in bone marrow-derived macrophages followed by propagation in grivet monkey Marc-145 cells. Furthermore, 28 PRRSV-positive samples and 20 cell-adapted viruses were selected for high-throughput sequencing (HTS) to obtain the entire PRRSV genome sequences. Phylogenetic analysis based on the nucleotide sequences of the ORF5 gene of the PRRSV strains identified in this study grouped into sub-lineages 1.8 and 8.7 the former being the dominant strain currently circulating in Xinjiang. However, the NSP2 proteins of the Xinjiang PRRSV strains shared the same deletion patterns as sub-lineage 1.8 prototype strain NADC30 with the exception of 4 strains carrying 2-3 additional amino acid deletions. Further analysis confirmed that recombination events had occurred in 27 of 37 PRRSVs obtained here with the parental strains belonging to sub-lineages 1.8 and 8.7, lineages 3 and 5, with the recombination events having occurred most frequently in the 5' and 3' termini of ORF1a and 5' terminus of ORF1b.

12.
Drug Des Devel Ther ; 18: 1855-1864, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38828023

RESUMEN

Purpose: Henagliflozin is an original, selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. Hydrochlorothiazide (HCTZ) is a common anti-hypertensive drug. This study aimed to evaluate the potential interaction between henagliflozin and HCTZ. Methods: This was a single-arm, open-label, multi-dose, three-period study that was conducted in healthy Chinese volunteers. Twelve subjects were treated in three periods, period 1: 25 mg HCTZ for four days, period 2: 10 mg henagliflozin for four days and period 3: 25 mg HCTZ + 10 mg henagliflozin for four days. Blood samples and urine samples were collected before and up to 24 hours after drug administrations on day 4, day 10 and day 14. The plasma concentrations of henagliflozin and HCTZ were analyzed using LC-MS/MS. The urine samples were collected for pharmacodynamic glucose and electrolyte analyses. Tolerability was also evaluated. Results: The 90% CI of the ratio of geometric means (combination: monotherapy) for AUCτ,ss of henagliflozin and HCTZ was within the bioequivalence interval of 0.80-1.25. For henagliflozin, co-administration increased Css, max by 24.32% and the 90% CI of the GMR was (108.34%, 142.65%), and the 24-hour urine volume and glucose excretion decreased by 0.43% and 19.6%, respectively. For HCTZ, co-administration decreased Css, max by 19.41% and the 90% CI of the GMR was (71.60%, 90.72%), and the 24-hour urine volume and urinary calcium, potassium, phosphorus, chloride, and sodium excretion decreased by 11.7%, 20.8%, 11.8%, 11.9%, 22.0% and 15.5%, respectively. All subjects (12/12) reported adverse events (AEs), but the majority of theses AEs were mild and no serious AEs were reported. Conclusion: Although Css,max was affected by the combination of henagliflozin and HCTZ, there was no clinically meaningful safety interaction between them. Given these results, coadministration of HCTZ should not require any adaptation of henagliflozin dosing. Trial Registration: ClinicalTrials.gov NCT06083116.


Asunto(s)
Interacciones Farmacológicas , Voluntarios Sanos , Hidroclorotiazida , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Pueblo Asiatico , Relación Dosis-Respuesta a Droga , Pueblos del Este de Asia , Glucósidos/administración & dosificación , Glucósidos/farmacocinética , Glucósidos/farmacología , Hidroclorotiazida/administración & dosificación , Hidroclorotiazida/farmacocinética , Hidroclorotiazida/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/administración & dosificación , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacocinética , China
13.
Arch Gynecol Obstet ; 310(2): 695-704, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38852111

RESUMEN

BACKGROUND: Left-right laterality disorders are a heterogeneous group of disorders caused by an altered position or orientation of the thoracic and intra-abdominal organs and vasculature across the left-right axis. They mainly include situs inversus and heterotaxy. Those disorders are complicated by cardiovascular abnormalities significantly more frequently than situs solitus. METHODS: In this study, 16 patients with a fetal diagnosis of laterality disorder with congenital heart defects (CHD) were evaluated with a single nucleotide polymorphism array (SNP-arry) combined with whole-exome sequencing (WES). RESULTS: Although the diagnostic rate of copy number variations was 0 and the diagnostic rate of WES was 6.3% (1/16), the likely pathogenic gene DNAH11 and the candidate gene OFD1 were ultimately identified. In addition, novel compound heterozygous mutations in the DNAH11 gene and novel hemizygous variants in the OFD1 gene were found. Among the combined CHD, a single atrium/single ventricle had the highest incidence (50%, 8/16), followed by atrioventricular septal defects (37.5%, 6/16). Notably, two rare cases of common pulmonary vein atresia (CPVA) were also found on autopsy. CONCLUSION: This study identified the types of CHD with a high incidence in patients with laterality disorders. It is clear that WES is an effective tool for diagnosing laterality disorders and can play an important role in future research.


Asunto(s)
Dineínas Axonemales , Secuenciación del Exoma , Cardiopatías Congénitas , Mutación , Humanos , Femenino , Embarazo , Cardiopatías Congénitas/genética , Cardiopatías Congénitas/diagnóstico , Dineínas Axonemales/genética , Diagnóstico Prenatal/métodos , Heterocigoto , Situs Inversus/genética , Situs Inversus/diagnóstico , Situs Inversus/diagnóstico por imagen , Polimorfismo de Nucleótido Simple , Adulto , Síndrome de Heterotaxia/genética , Síndrome de Heterotaxia/diagnóstico por imagen
14.
Chemistry ; 30(51): e202402095, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-38943462

RESUMEN

In the cross-plane single-molecule junctions, the correlation between molecular aromaticity and conductance remained puzzling. Cross-plane break junction (XPBJ) provides new insight into understanding the role of aromaticity and conjugation to molecules on charge transport through the planar molecules. In this work, we investigated the modulation of cross-plane charge transport in pyrene derivatives by hydrogenation and substituents based on the XPBJ method that differs from those used in-plane transport. We measured the electrical conductance of the hydrogenated derivatives of the pyrenes and found that hydrogenation reduces conductance, and the fully hydrogenated molecule has the lowest conductance. Conductance of pyrene derivatives increased after substitution by both electron-donating and electron-withdrawing groups. By calculating, the trend in decreased conductance of hydrogenated pyrene was found to be consistent with the change in aromaticity. Electron-withdrawing substituents reduce the aromaticity of the molecule and narrow the HOMO-LUMO gap, while electron-donating groups increase the aromaticity but also narrow the gap. Our work reveals the potential of fine-tuning the structure of the pyrene molecule to control the cross-plane charge transport through the single-molecule junctions.

15.
Front Pharmacol ; 15: 1359939, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38933676

RESUMEN

Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and pharmacodynamic profile of HEC95468, a soluble guanylate cyclase (sGC) stimulator, in healthy volunteers. Sixty-two, eighteen, and forty-eight participants were enrolled in the single ascending dose (SAD) study, the food effect (FE) study, and the multiple ascending dose (MAD) study, respectively. The study conforms to good clinical practice and the Declaration of Helsinki. Overall, HEC95468 was safe and tolerable; a higher proportion of HEC95468-treated participants reported mild headaches, dizziness, decreased blood pressure, increased heart rate, and gastrointestinal-related treatment-emergent adverse events (TEAEs), similar to the sGC stimulators riociguat and vericiguat. In terms of pharmacokinetic parameters, the maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-t) were dose-proportional over the dose range. Moderate accumulation was observed after multiple administrations of HEC95468. Systolic blood pressure (SBP) and diastolic blood pressure decreased, while 3',5'-cyclic guanosine monophosphate (cGMP) concentration in plasma increased and heart rate was induced. Vasoactive hormones (renin, angiotensin II, and norepinephrine) in plasma were compensatorily elevated after oral administration. These data supported further clinical trials of HEC95468 in the treatment of heart failure and pulmonary arterial hypertension. Systematic Review Registration: http://www.chinadrugtrials.org.cn, identifier CTR20210064.

16.
J Phys Chem B ; 128(27): 6638-6647, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38922305

RESUMEN

Studying the hydrogen bonding structure of H2O at the metal-water interface is a highly complex yet fascinating endeavor. The intricate interactions and diverse orientations of water molecules on metal surfaces with varying potentials pose a significant challenge in elucidating the coupling between O-H stretching and H-O-H bending modes. In this study, we employed DFT-MD simulation to explore how the orientation of interfacial water molecules changes with the applied potential on the Au(111) surface. Based on the surface-specific velocity-velocity correlation function (ssVVCF) formula, we calculated vibrational sum frequency generation (VSFG) spectra for the O-H stretches. We found that three assigned peaks (∼3300, ∼3450, and 3650 cm-1) shifted toward lower frequencies as the potential moved toward more negative values. Our results align remarkably well with experimental Raman spectroscopy data. Notably, our VSFG analysis revealed a significant change in the VSFG spectra of the hydrogen-bonded O-H groups (∼3300 cm-1), switching from a negative to a positive sign with decreasing potential. This alteration suggests a substantial change in the orientation of these low-frequency O-H groups owing to their increased interactions with the Au surface. In contrast, the orientations of both the high-frequency O-H groups (∼3450 cm-1) and the dangling O-H groups (∼3650 cm-1) remained unaffected by the applied potentials. Furthermore, our analysis of the decomposed vibrational density of states (VDOS) for the H-O-H bending mode uncovered the coupling between the H-O-H bending and O-H stretching vibrations, known as the Fermi resonance. Our work suggests that the H-O-H bending vibration becomes restricted when water molecules transition from the ″one-H-down″ to the ″two-H-down″ conformation, leading to a redshift in the O-H stretching vibration through the Fermi resonance. By constructing the VSFG and decomposed VDOS spectra, we gained valuable insights into the structural changes that Raman spectra alone cannot fully interpret. Specifically, our analysis revealed the critical role of the Fermi resonance effect in shaping the spectroscopic signature of interfacial water molecules on the Au(111) surface.

17.
Ann Diagn Pathol ; 73: 152357, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38941945

RESUMEN

Upper tract urothelial carcinoma (UTUC) is a relatively rare yet aggressive malignancy. While radical nephroureterectomy (RNU) remains the cornerstone treatment, UTUC has high local and metastatic relapse rates, leading to a dismal prognosis. To identify the clinicopathological factors associated with an increased risk of local and metastatic relapse in UTUC, we conducted a retrospective analysis of 133 consecutive UTUC patients who underwent RNU from 1998 to 2018. Patients lost to follow-up or with a history of bladder cancer were excluded from the study. The remaining 87 patients were categorized into two subgroups: those with tumor recurrence/relapse (40 cases) and those without recurrence/relapse (47 cases). Clinical and pathological characteristics were compared across the two groups. Multiple factors are associated with UTUC recurrence/relapse including larger tumor size, histology divergent differentiations/subtypes, high tumor grade, advanced pathologic T stage, positive margin, lymphovascular invasion (LVI), positive lymph node status, and preoperative hydronephrosis. Multivariate Cox regression analysis revealed that squamous differentiation predicted recurrence/relapse (p = 0.012), independent of tumor stage. Moreover, compared to the conventional histology type, UTUC with squamous differentiation had a significantly higher relapse rate (p = 0.0001) and poorer survival (p = 0.0039). This observation was further validated in invasive high-grade UTUC cases. Our findings suggest that many pathological factors contribute to UTUC recurrence/relapse, particularly, squamous differentiation may serve as an independent risk predictor for relapse and a potent prognosticator for adverse cancer-specific survival in UTUC patients. Recognizing and thoroughly assessing the pathological factors is essential for better oncologic management of UTUC.

18.
Hum Vaccin Immunother ; 20(1): 2357238, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38869047

RESUMEN

This study assessed the knowledge of 12- to 15-year-old male junior high school students of HPV and HPV vaccines and their willingness to be vaccinated against it. From March to May 2023, students from six junior high schools in Zhejiang Province were randomly selected to complete an online, anonymous, self-administered questionnaire. Of the 1786 students, 618 (34.6%) reported knowledge of HPV vaccine. In general, junior high school boys have low general knowledge about HPV, the consequences of HPV infection, and the effects of HPV vaccination. Multivariate analysis showed that the subgroup scoring 6-7 on the measure of the consequences of HPV infection(7 questions with 1 score for each correct answer) compared to the subgroup scoring 0, the subgroups scoring 2 and 3 on the measure of the preventive effect of HPV vaccine(3 questions with 1 score for each correct answer) compared to the subgroup scoring 0 were were more likely to be willing to be vaccinated against HPV. Hearing that someone close to them had cancer, believing that men also need to be vaccinated against HPV, knowing that someone close to them had been vaccinated against HPV, and being concerned about cervical cancer in their female sexual partners were all more likely to generate positive responses. HPV vaccine education for this group of students should emphasize the possibility and consequences of HPV infection in males, along with the importance and benefits of HPV vaccination; actual cases of vaccination in students around them can be used to achieve this goal.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Aceptación de la Atención de Salud , Estudiantes , Vacunación , Humanos , Masculino , Vacunas contra Papillomavirus/administración & dosificación , Adolescente , China , Infecciones por Papillomavirus/prevención & control , Estudiantes/psicología , Encuestas y Cuestionarios , Aceptación de la Atención de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/psicología , Vacunación/psicología , Vacunación/estadística & datos numéricos , Niño , Neoplasias del Cuello Uterino/prevención & control , Femenino , Instituciones Académicas
19.
Small ; 20(37): e2401315, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38747008

RESUMEN

Battery-type electrode materials with high capacity, wide potential windows, and good cyclic stability are crucial to breaking through energy storage limitations and achieving high energy density. Herein, a novel 2D-on-2D Al-doped NiCo layered double hydroxide (NiCoAlx LDH) nanosheet arrays with high-mass-loading are grown on a carbon cloth (CC) substrate via a two-step hydro/solvothermal deposition strategy, and the effect of Al doping is employed to modify the deposition behavior, hierarchical morphology, phase stability, and multi-metallic synergistic effect. The optimized NiCoAl0.1 LDH electrode exhibits capacities of 5.43, 6.52, and 7.25 C cm-2 (9.87, 10.88, and 11.15 F cm-2) under 0-0.55, 0-0.60, and 0-0.65 V potential windows, respectively, illustrating clearly the importance of the wide potential window. The differentiated deposition strategy reduces the leaching level of Al3+ cations in alkaline solutions, ensuring excellent cyclic performance (108% capacity retention after 40 000 cycles). The as-assembled NiCoAl0.1 LDH//activated carbon cloth (ACC) hybrid supercapacitor delivers 3.11 C cm-2 at 0-2.0 V, a large energy density of 0.84 mWh cm-2 at a power density of 10.00 mW cm-2, and excellent cyclic stability with ≈135% capacity retention after 150 000 cycles.

20.
Environ Sci Technol ; 58(21): 9082-9090, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38743497

RESUMEN

This prospective birth cohort study evaluated the association of exposure to PM2.5 (diameter ≤2.5 µm), PM1-2.5 (1-2.5 µm), and PM1 (≤1 µm) with maternal thyroid autoimmunity and function during early pregnancy. A total of 15,664 pregnant women were included at 6 to 13+6 gestation weeks in China from 2018 to 2020. Single-pollutant models using generalized linear models (GLMs) showed that each 10 µg/m3 increase in PM2.5 and PM1-2.5 was related with 6% (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.01, 1.12) and 15% (OR = 1.15, 95% CI: 1.08, 1.22) increases in the risk of thyroid autoimmunity, respectively. The odds of thyroid autoimmunity significantly increased with each interquartile range increase in PM2.5 and PM1-2.5 exposure (P for trend <0.001). PM1 exposure was not significantly associated with thyroid autoimmunity. GLM with natural cubic splines demonstrated that increases in PM2.5 and PM1-2.5 exposure were associated with lower maternal FT4 levels, while a negative association between PM1 and FT4 levels was found when exposure exceeded 32.13 µg/m3. Only PM2.5 exposure was positively associated with thyrotropin (TSH) levels. Our findings suggest that high PM exposure is associated with maternal thyroid disruption during the early pregnancy.


Asunto(s)
Autoinmunidad , Material Particulado , Glándula Tiroides , Humanos , Femenino , Embarazo , Adulto , China , Estudios Prospectivos , Contaminantes Atmosféricos , Exposición Materna
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