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1.
Mol Pharm ; 21(5): 2238-2249, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38622497

RESUMEN

Tuberculosis (TB) is a chronic disease caused byMycobacterium tuberculosis (Mtb), which shows a long treatment cycle often leads to drug resistance, making treatment more difficult. Immunogens present in the pathogen's cell membrane can stimulate endogenous immune responses. Therefore, an effective lipid-based vaccine or drug delivery vehicle formulated from the pathogen's cell membrane can improve treatment outcomes. Herein, we extracted and characterized lipids fromMycobacterium smegmatis, and the extracts contained lipids belonging to numerous lipid classes and compounds typically found associated with mycobacteria. The extracted lipids were used to formulate biomimetic lipid reconstituted nanoparticles (LrNs) and LrNs-coated poly(lactic-co-glycolic acid) nanoparticles (PLGA-LrNs). Physiochemical characterization and results of morphology suggested that PLGA-LrNs exhibited enhanced stability compared with LrNs. And both of these two types of nanoparticles inhibited the growth of M. smegmatis. After loading different drugs, PLGA-LrNs containing berberine or coptisine strongly and synergistically prevented the growth of M. smegmatis. Altogether, the bacterial membrane lipids we extracted with antibacterial activity can be used as nanocarrier coating for synergistic antibacterial treatment of M. smegmatis─an alternative model of Mtb, which is expected as a novel therapeutic system for TB treatment.


Asunto(s)
Mycobacterium smegmatis , Nanopartículas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Nanopartículas/química , Mycobacterium smegmatis/efectos de los fármacos , Lípidos/química , Sinergismo Farmacológico , Membrana Celular/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/efectos de los fármacos , Antituberculosos/farmacología , Antituberculosos/química , Antituberculosos/administración & dosificación , Mycobacterium/efectos de los fármacos , Berberina/farmacología , Berberina/química , Portadores de Fármacos/química , Tuberculosis/tratamiento farmacológico
2.
Environ Sci Technol ; 58(5): 2554-2563, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38266240

RESUMEN

Rapid and in situ identification of specific polymers is a challenging and crucial step in plastic recycling. However, conventional techniques continue to exhibit significant limitations in the rapid and field classification of plastic products, especially with the wide range of commercially available color polymers because of their large size, high energy consumption, and slow and complicated analysis procedures. In this work, a simple analytical system integrating a miniature and low power consumption (22.3 W) pyrolyzer (Pyr) and a low temperature, atmospheric pressure point discharge optical emission spectrometer (µPD-OES) was fabricated for rapidly identifying polymer types. Plastic debris is decomposed in the portable pyrolyzer to yield volatile products, which are then swept into the µPD-OES instrument for monitoring the optical emission patterns of the thermal pyrolysis products. With machine learning, five extensively used raw polymers and their consumer plastics were classified with an accuracy of ≥97.8%. Furthermore, the proposed method was applied to the identification of the aged polymers and plastic samples collected from a garbage recycling station, indicating its great potential for identification of environmentally weathered plastics. This portable Pyr-µPD-OES system provides a cost-effective tool for rapid and field identification of polymer types of recycled plastic for proper management and resource recycling.


Asunto(s)
Plásticos , Pirólisis , Plásticos/análisis , Polímeros , Reciclaje , Aprendizaje Automático
3.
BMC Oral Health ; 24(1): 754, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38951770

RESUMEN

OBJECTIVES: This study investigated the effectiveness of a deep convolutional neural network (CNN) in diagnosing and staging caries lesions in quantitative light-induced fluorescence (QLF) images taken by a self-manufactured handheld device. METHODS: A small toothbrush-like device consisting of a 400 nm UV light-emitting lamp with a 470 nm filter was manufactured for intraoral imaging. A total of 133 cases with 9,478 QLF images of teeth were included for caries lesion evaluation using a CNN model. The database was divided into development, validation, and testing cohorts at a 7:2:1 ratio. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC) were calculated for model performance. RESULTS: The overall caries prevalence was 19.59%. The CNN model achieved an AUC of 0.88, an accuracy of 0.88, a specificity of 0.94, and a sensitivity of 0.64 in the validation cohort. They achieved an overall accuracy of 0.92, a sensitivity of 0.95 and a specificity of 0.55 in the testing cohort. The model can distinguish different stages of caries well, with the best performance in detecting deep caries followed by intermediate and superficial lesions. CONCLUSIONS: Caries lesions have typical characteristics in QLF images and can be detected by CNNs. A QLF-based device with CNNs can assist in caries screening in the clinic or at home. TRIAL REGISTRATION: The clinical trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2300073487, Date: 12/07/2023).


Asunto(s)
Caries Dental , Redes Neurales de la Computación , Fluorescencia Cuantitativa Inducida por la Luz , Humanos , Caries Dental/diagnóstico , Caries Dental/diagnóstico por imagen , Femenino , Fluorescencia Cuantitativa Inducida por la Luz/instrumentación , Masculino , Adulto , Sensibilidad y Especificidad , Persona de Mediana Edad , Adolescente , Adulto Joven , Curva ROC
4.
Chem Rev ; 121(18): 11458-11526, 2021 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-33370102

RESUMEN

Type 1 diabetes therapies that afford tighter glycemic control in a more manageable and painless manner for patients has remained a central focus of next-generation diabetes therapies. In many of these emerging technologies, namely, self-regulated insulin delivery and cell replacement therapies, hydrogels are employed to mitigate some of the most long-standing challenges. In this Review, we summarize recent developments in the use of hydrogels for both insulin delivery and insulin-producing cell therapies for type 1 diabetes management. We first outline perspectives in glucose sensitive hydrogels for smart insulin delivery, pH sensitive polymeric hydrogels for oral insulin delivery, and other physiochemical signals used to trigger insulin release from hydrogels. We, then, investigate the use of hydrogels in the encapsulation of insulin secreting cells with a special emphasis on hydrogels designed to mitigate the foreign body response, provide a suitable extracellular microenvironment, and improve mass transfer through oxygen supplementation and vascularization. Evaluations of limitations and promising directions for future research are also considered. Continuing interdisciplinary and collaborative research efforts will be required to produce hydrogels with instructive biochemical microenvironments necessary to address the enduring challenges of emerging type 1 diabetes therapies.


Asunto(s)
Diabetes Mellitus Tipo 1 , Hidrogeles , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucosa/metabolismo , Humanos , Insulina , Polímeros
5.
J Clin Periodontol ; 50(2): 183-199, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36089906

RESUMEN

AIM: The regulation of osteoclasts (OCs) by inhibitory immunoreceptors maintains bone homeostasis and is considered an important determinant of the extent of periodontal pathology. The aim of this study was to investigate the role of the inhibitory immunoreceptor CD300lf and its ligand ceramide in osteoclastogenesis in periodontitis. MATERIALS AND METHODS: The expression of CD300lf was measured in vitro and in a ligature-induced periodontitis model. The effect of CD300lf ablation on osteoclastogenesis was examined in ligature-retained and ligature removal periodontitis models. The effect of ceramide, the ligand of CD300lf, was examined in osteoclastogenesis in vitro and in vivo by smearing 20 µg of ceramide dissolved in carboxymethylcellulose on teeth and gingiva every other day in an experimental periodontitis model and ligature removal model. RESULTS: CD300lf expression was downregulated during osteoclastogenesis. Ablation of CD300lf in the ligature-induced periodontitis model increased the number of OCs and exacerbated bone damage. Bone resorption caused by CD300lf ablation was reversible following ligature removal. CD300lf-ceramide binding suppressed osteoclastogenesis in vitro and inhibited alveolar bone loss in a mouse periodontitis model. CONCLUSIONS: Our findings reveal that CD300lf-ceramide binding plays a critical negative role in alveolar bone loss in periodontitis by inhibiting OCs differentiation.


Asunto(s)
Pérdida de Hueso Alveolar , Periodontitis , Animales , Ratones , Pérdida de Hueso Alveolar/prevención & control , Pérdida de Hueso Alveolar/patología , Ligandos , Osteoclastos , Osteogénesis , Periodontitis/metabolismo , Ligando RANK/metabolismo , Ceramidas/metabolismo
6.
Oral Dis ; 29(8): 3472-3480, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36070195

RESUMEN

OBJECTIVES: Hemifacial microsomia (HFM) is a common birth defect involving the first and second branchial arch derivatives. Although several chromosomal abnormalities and causal gene variants have been identified, genetic etiologies in a majority of cases with HFM remain unknown. This study aimed to identify genetic mutations in affected individuals with HFM. METHODS: Whole-exome sequencing and bioinformatics analysis were performed for 16 affected individuals and their family members. Sanger sequencing was applied for confirmation of selected mutations. Zebrafish embryos were used for in situ hybridization of candidate gene, microinjection with antisense morpholino, and cartilage staining. RESULTS: A homozygous missense mutation (c.484G > A; p.V162I) in the FRK gene was identified in an 18-year-old girl with HFM and dental abnormalities. Heterozygous mutation of this mutation was identified in her parents, who are first cousins in a consanguineous family. FRK is highly expressed in the Meckel's cartilage during embryonic development in mouse and zebrafish. Knockdown of frk in zebrafish showed a lower length and width ratio of Meckel's cartilage, abnormal mandibular jaw joint, and disorganized ceratobranchial cartilage and bone. CONCLUSIONS: We identified a recessive variant in the FRK gene as a novel candidate gene for a patient with HFM and mandibular hypoplasia and revealed its effects on craniofacial and embryonic development in zebrafish.


Asunto(s)
Síndrome de Goldenhar , Humanos , Femenino , Ratones , Animales , Adolescente , Síndrome de Goldenhar/genética , Pez Cebra/genética , Mandíbula/anomalías , Articulación Temporomandibular , Cartílago , Proteínas de Neoplasias , Proteínas Tirosina Quinasas
7.
Eur J Dent Educ ; 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37908172

RESUMEN

INTRODUCTION: Undergraduate dental students frequently have reduced clinical experience which presents a challenge for their dental education. Previously, we developed a virtual reality (VR) simulating the whole clinical treatment process of a patient with angle Class II division 1 malocclusion, and the VR also helped to explain some important orthodontic concepts. As a novel teaching tool, this study aims to compare the effects of VR versus traditional case analysis by Power Point (PPT) in inspiring student learning motivation and evaluating learning experience. MATERIALS AND METHODS: A randomized, cross-over, stratified sampling method was taken to divide the fourth-year undergraduate dental students equally into two groups. The two groups were crossed over to use VR and PPT. RESULTS: For the whole study, results indicated that students in the VR group showed higher learning motivation (including attention, relevance, confidence and satisfaction) than in the PPT group, but the differences between VR and PPT groups were not very big, and the median of the differences located at 0. For learning experience, students thought VR to be more useful, more enjoyable and more engaging, but the median of differences also located at 0. Notably, the majority of students had higher recommendations for VR than PPT, and the median difference located at 1. However, when the two phases were analysed separately, some items showed no significant differences between VR and PPT learning. CONCLUSION: VR is a very useful adjunct to education compared to traditional case analysis by PPT, but we cannot exaggerate its benefits. Educators should make good use of VR to solve the difficult problems in education.

8.
J Nanobiotechnology ; 20(1): 318, 2022 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-35794597

RESUMEN

Cerebral malaria (CM) is a life-threatening neurological complication caused by Plasmodium falciparum. About 627,000 patients died of malaria in 2020. Currently, artemisinin and its derivatives are the front-line drugs used for the treatment of cerebral malaria. However, they cannot target the brain, which decreases their effectiveness. Therefore, increasing their ability to target the brain by the nano-delivery system with brain-targeted materials is of great significance for enhancing the effects of antimalarials and reducing CM mortality. This study used glucose transporter 1 (GLUT1) on the blood-brain barrier as a target for a synthesized cholesterol-undecanoic acid-glucose conjugate. The molecular dynamics simulation found that the structural fragment of glucose in the conjugate faced the outside the phospholipid bilayers, which was conducive to the recognition of brain-targeted liposomes by GLUT1. The fluorescence intensity of the brain-targeted liposomes (na-ATS/TMP@lipoBX) in the mouse brain was significantly higher than that of the non-targeted liposomes (na-ATS/TMP@lipo) in vivo (P < 0.001) after intranasal administration. The infection and recurrence rate of the mice receiving na-ATS/TMP@lipoBX treatment were significantly decreased, which had more advantages than those of other administration groups. The analysis of pharmacokinetic data showed that na-ATS/TMP@lipoBX could enter the brain in both systemic circulation and nasal-brain pathway to treat malaria. Taken together, these results in this study provide a new approach to the treatment of cerebral malaria.


Asunto(s)
Malaria Cerebral , Nanocompuestos , Animales , Glucosa/química , Transportador de Glucosa de Tipo 1 , Liposomas/química , Malaria Cerebral/tratamiento farmacológico , Ratones
9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(3): 409-413, 2022 May.
Artículo en Zh | MEDLINE | ID: mdl-35642147

RESUMEN

Objective: To study the virulence variation of enterovirus 71 (EV71) during thermal adaptive evolution, providing references for the prevention and control of the EV71-related hand, foot and mouth disease. Methods: Parental strains and thermal-adapted strains originating from EV71 sibling strains (lineage #100 and #101) were used for plaque assay validation, CCK-8 cytotoxicity experiment, and host proteomics studies after Vero cell infection. Plaque morphology and cell inhibition rate of the viral strains were obtained. Mass spectrometry was used to examine and analyze the functions of proteins that were differential expressed in the host cells. Results: Plaque morphology variation was found only in the heat-adapted strain of lineage #101. Increase in cell inhibition rate was observed in all the thermal-adapted strains, but the amount of increase varied in different strains. According to the results of clustering analysis and principal component analysis, after infection of Vero cells, the host cell protein profile of the heat-adapted strains was similar to that of the parental strains and the host cell protein profile of cold-adapted strains was similar to that of cell-adapted strains. It showed that 500 kinds of proteins presented inter-group difference in their expression, with 239 kinds being up-regulated proteins and 261 being down-regulated. The function of the up-regulated proteins were related to post-translational protein modification, while the functions of the down-regulated proteins were related to SRP-dependent cotranslational protein translocation/targeting to membrane and retrograde protein transport. Conclusion: Virulence variations of enterovirus 71 may accompany thermal adaptive evolution, but its mechanism of action still awaits further investigation.


Asunto(s)
Enterovirus Humano A , Infecciones por Enterovirus , Enterovirus , Animales , Chlorocebus aethiops , Enterovirus Humano A/genética , Células Vero , Virulencia
10.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4462-4468, 2022 Aug.
Artículo en Zh | MEDLINE | ID: mdl-36046876

RESUMEN

An ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method was established for the determination of active components of Sarcandrae Herba, and applied to the pharmacokinetics study of multiple dosage forms. After SD rats were administered by gavage with three dosage forms [Sarcandrae Herba extract, commercial Sarcandrae Herba Guttate Pills, and polydopamine guttate pills loaded with active components of Sarcandrae Herba(PDA-Sg Guttate Pills)], blood samples were collected from the inner canthus at different time points. After protein precipitation, plasma samples were separated on ACQUITY UPLC C_(18) column(2.1 mm×100 mm, 1.7 µm). The mobile phase consisted of water containing 0.2% formic acid and acetonitrile in gradient elution. The negative ions were measured simultaneously in the multi-reaction monitoring(MRM) mode. The pharmacokinetic parameters were calculated and fitted by DAS 2.0. All four components could be detected in the plasma of rats in each group at each time point except the neochlorogenic acid and cryptochlorogenic acid in the Sarcandrae Herba extract group. The guttate pills group showed a significant increase in drug content at each time point. The exposure of the main components of Sarcandrae Herba in blood was effectively increased by PDA-drug loading effect in PDA-Sg Guttate Pills(The AUC_(0-24 h) of neochlorogenic acid, cryptochlorogenic acid, isaziridin and rosmarinic acid reached 2.45, 32.90, 1.54, 4.81 times that of the commercial guttate pills). This study proves the measurability of the above-mentioned multi-component in vitro-in vivo delivery process. The pharmacokinetic study has shown that PDA-Sg Guttate Pills can effectively delay the elimination time and improve the bioavailability of the four components, which can provide theoretical data for the production of the drug.


Asunto(s)
Medicamentos Herbarios Chinos , Espectrometría de Masas en Tándem , Animales , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/farmacocinética , Indoles , Polímeros , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/métodos
11.
Clin Endocrinol (Oxf) ; 95(1): 153-162, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33548149

RESUMEN

OBJECTIVE: We aimed to analyse FGFR1 rare variants in a series of Chinese congenital hypogonadotropic hypogonadism (CHH) patients. In addition, we intended to understand the clinical characteristics and the response to treatment of CHH patients with FGFR1 rare variants. PATIENTS AND METHODS: A total of 357 CHH patients were recruited at Peking Union Medical College Hospital. We used Sanger sequencing to analyse FGFR1 gene. In silico analysis was carried out to study the pathogenicity of novel missense variants. The clinical, endocrinological and therapeutic effects from patients carrying FGFR1 rare variants were analysed retrospectively. RESULTS: Thimissense mutations.rty patients in this series were found to harbour 29 FGFR1 rare variants, with 8 recurrent and 21 novel variants. After comprehensive analysis, 18 out of 21 novel variants were classified as likely pathogenic (LP) ones. These variants are widely spread throughout the FGFR1 gene and almost all FGFR1 functional domains, which exhibited no hot spot. Cryptorchidism, cleft palate and dental abnormality incidence in this CHH series that possessed FGFR1 LP variants were approximately 38.5%, 7.6% and 3.8%, respectively. Among patients who accepted the fertility-promoting treatment, 8 out of 10 patients succeeded in spermatogenesis. CONCLUSIONS: Eighteen novel LP variants were found to expand the spectrum of FGFR1 rare variants. In CHH patients possessing FGFR1 variants, we found that the rate of spermatogenesis was high following fertility-promoting therapy and the existence of cryptorchidism may represent the underlying factors which affect spermatogenesis.


Asunto(s)
Hipogonadismo , Síndrome de Kallmann , Humanos , Hipogonadismo/tratamiento farmacológico , Hipogonadismo/genética , Síndrome de Kallmann/tratamiento farmacológico , Síndrome de Kallmann/genética , Masculino , Mutación , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Estudios Retrospectivos , Espermatogénesis
12.
BMC Cancer ; 21(1): 1301, 2021 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-34872507

RESUMEN

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is an improved formulation of doxorubicin with comparable effectiveness but significantly lower cardiotoxicity than conventional anthracycline. This study aimed to evaluate the real-world effectiveness and safety of PLD versus epirubicin as neoadjuvant or adjuvant treatment for breast cancer. METHODS: Clinical data of invasive breast cancer patients who received neoadjuvant or adjuvant chemotherapy with PLD or epirubicin were retrospectively collected. Propensity score matching (PSM) was performed to reduce the risk of selection bias. The molecular typing of these patients included Luminal A, Luminal B, HER2-positive, and basal-like/triple-negative. The primary outcome was pathological complete response (pCR) rate for neoadjuvant chemotherapy and 3-year disease-free survival (DFS) rate for adjuvant chemotherapy. Noninferiority was suggested if the lower limit of the 95% CI for the 3-year DFS rate difference was greater than - 10%. The secondary outcome was adverse reactions. RESULTS: A total of 1213 patients were included (neoadjuvant, n = 274; adjuvant, n = 939). pCR (ypT0/Tis ypN0) rates of patients who received neoadjuvant chemotherapy were 11.6% for the PLD group and 7.0% for the epirubicin group, but the difference was not statistically significant (P = 0.4578). The 3-year DFS rate of patients who received adjuvant chemotherapy was 94.9% [95%CI, 91.1-98.6%] for the PLD group and 95.4% [95%CI, 93.0-97.9%] for the epirubicin group (P = 0.5684). Rate difference between the two groups and its 95% CI was - 0.55 [- 5.02, 3.92]. The lower limit of the 95% CI was - 5.0% > - 10.0%, suggesting that PLD is not be inferior to epirubicin in adjuvant chemotherapy for breast cancer. The incidences of myelosuppression, decreased appetite, alopecia, gastrointestinal reactions, and cardiotoxicity were lower in the PLD group than in the epirubicin group, while the incidence of nausea was higher in the PLD group. CONCLUSIONS: In the neoadjuvant and adjuvant treatment of breast cancer, effectiveness is similar but toxicities are different between the PLD-containing regimen and epirubicin-containing regimen. Therefore, further study is warranted to explore PLD-based neoadjuvant and adjuvant chemotherapy for breast cancer.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante/métodos , Doxorrubicina/análogos & derivados , Epirrubicina/uso terapéutico , Terapia Neoadyuvante/métodos , Adulto , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Epirrubicina/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polietilenglicoles/farmacología , Polietilenglicoles/uso terapéutico
13.
Physiol Plant ; 173(3): 961-977, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34237150

RESUMEN

Paeonia is recognized globally due to its ornamental value. However, the mechanisms behind the formation of distinct levels of lignification in Paeonia stems remain largely unknown. In this study, we selected three representative Paeonia species, namely P. ostii (shrub), P. lactiflora (herb), and P. × 'Hexie' (semi-shrub), to evaluate and contrast their respective anatomical structure, phytochemical composition and transcriptomic profile. Our results showed that the degree of lignin deposition on the cell wall, along with the total amount of lignin and its monomers (especially G-lignin) were higher in P. ostii stems compared to the other two species at almost all development stages except 80 days after flowering. Furthermore, we estimated a total number of unigenes of 60,238 in P. ostii, 43,563 in P. × 'Hexie', and 40,212 in P. lactiflora from stem transcriptome. We then built a co-expression network of 25 transcription factors and 21 enzyme genes involved in lignin biosynthesis and identified nine key candidate genes. The expression patterns of these genes were positively correlated with the transcription levels of PAL, C4H, 4CL2, CCR, and COMT, as well as lignin content. Moreover, the highest relative expression levels of CCR, 4CL2, and C4H were found in P. ostii. This study provides an explanation for the observed differences in lignification between woody and herbaceous Paeonia stems, and constitutes a novel reference for molecular studies of stem-specific lignification process and lignin biosynthesis that can impact the ornamental industry.


Asunto(s)
Paeonia , Pared Celular/genética , Pared Celular/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Lignina/metabolismo , Paeonia/genética , Paeonia/metabolismo , Transcriptoma/genética
14.
JAMA ; 325(1): 50-58, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33300950

RESUMEN

Importance: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed. Objective: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. Design, Setting, and Participants: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. Interventions: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. Main Outcomes and Measures: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. Results: Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. Conclusions and Relevance: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT01112826.


Asunto(s)
Capecitabina/administración & dosificación , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Capecitabina/efectos adversos , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Estudios de Seguimiento , Síndrome Mano-Pie/etiología , Humanos , Quimioterapia de Mantención , Mastectomía , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasia Residual , Observación , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/cirugía
15.
Exp Cell Res ; 383(1): 111496, 2019 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-31306654

RESUMEN

Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide, and there is currently no effective therapeutic strategy in clinical practice. Gene therapy has great potential for decreasing tumor-induced mortality but has been clinically limited because of the lack of tumor-specific targets and insufficient gene transfer. The study of targeted transport of therapeutic genes in HCC treatment seems to be very important. In this study, we evaluated a gene therapy approach targeting HCC using the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene system in HCC cell lines and in an in vivo human HCC xenograft mouse model. GP73-modified liposomes targeted gene delivery to the tumor tissue, and the survivin promoter drove HSVtk expression in the HCC cells. Our results showed that the survivin promoter was specifically activated in tumor cells and HSVtk was expressed selectively in tumor cells. Combined with GCV treatment, HSVtk expression resulted in suppression of HCC cell proliferation via enhancing apoptosis. Moreover, tail vein injection of GP73-HSVtk significantly suppressed the growth of xenograft tumors through an apoptosis-dependent pathway and extended the survival of tumor-bearing mice without damaging the mice liver functions. Taken together, this study demonstrates an effective cancer-specific gene therapy strategy using the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene system for HCC that can be further developed for future clinical trials.


Asunto(s)
Carcinoma Hepatocelular/terapia , Terapia Genética , Liposomas/administración & dosificación , Neoplasias Hepáticas/terapia , Proteínas de la Membrana/química , Survivin/genética , Timidina Quinasa/genética , Animales , Apoptosis , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Proliferación Celular , Femenino , Ganciclovir/administración & dosificación , Vectores Genéticos/administración & dosificación , Humanos , Liposomas/química , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Regiones Promotoras Genéticas , Simplexvirus/enzimología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
16.
BMC Med Educ ; 20(1): 474, 2020 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-33243248

RESUMEN

BACKGROUND: English education in professional areas has become more and more important with the increasing internationalization of health profession education in countries around the world. In this study, we aimed to evaluate current Chinese stomatology English education based on Chinese participants' ability to apply stomatology English during an international stomatology skill competition called the 'Guanghua Cup activity'. METHODS: The registration rate of English and Chinese volunteers and the answer rate and accuracy of Chinese and international contestants on the English knowledge quiz were statistically described. A five-point Likert scale questionnaire was delivered to all participants. The data were analyzed using the Spearman test, Kruskal-Wallis rank sum test and Mann-Whitney U test. RESULTS: Among the 194 students, the English and Chinese volunteer registration rate was 7.73 and 30.93%, respectively. The answer rate of Chinese contestants and international contestants in the English quiz was 25 and 75%, with an accuracy rate of 50 and 66.70%, respectively. The questionnaire was graded by Likert five-level classification. There was a positive correlation between the use of English textbooks in classes and the communication with international teachers and students in the competition (Rs = 0.348, p = 0.016). English volunteers had more preparation in English before the competition, more opportunities to communicate with international peers, and greater improvement in English ability than the contestants and Chinese volunteers (p < 0.001). After the competition, all participants paid more attention to stomatology English (p < 0.001). CONCLUSIONS: Chinese stomatology students have difficulty in stomatology English application. The 'Guanghua Cup' helps to improve English proficiency of English volunteers and arouses the interest of stomatology English for all participants. Chinese stomatology school needs to strengthen and reach a consensus in stomatology English education.


Asunto(s)
Medicina Oral , China , Competencia Clínica , Humanos , Estudiantes , Encuestas y Cuestionarios
17.
Aesthetic Plast Surg ; 44(2): 558-569, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31832737

RESUMEN

BACKGROUND: Capsular contracture, mainly caused by Staphylococcus epidermidis (S. epidermidis) biofilm formation, is a complex problem for breast cancer patients who undergo surgical prosthetic breast reconstruction. Estradiol has been reported to be involved in the formation of bacterial biofilms. Thus, the underlying mechanism of estradiol in capsular contracture needs to be investigated. METHODS: Biofilm-related gene expressions were measured by qRT-PCR after sterilizing the silicone with bacterial suspension and E2 treatment in vitro. Rat models were established with bilateral ovariectomy operations and estradiol subcutaneous injections. The effects of estradiol on capsular contracture were detected by monitoring serum estradiol levels, bacterial infection rate in organs, biofilm formation and capsular contracture in vivo; inflammatory factors in vivo were examined as well. Biofilm on the silicone implants was observed under a scanning electron microscope. RESULTS: Both positive regulatory genes and negative regulatory genes were increased by the high concentration of estradiol, suggesting that estradiol can promote the formation of biofilm by not only positive but also negative regulations. High estradiol levels increased bacterial infection rate in organs, biofilm formation and capsular contracture. Further, high estradiol caused a large number of inflammatory cells to infiltrate and caused serious inflammatory reactions that aggravate the immune imbalances of the host. CONCLUSION: High estradiol levels contribute to increasing capsular contracture caused by S. epidermidis biofilm formation. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.


Asunto(s)
Implantes de Mama , Mamoplastia , Animales , Implantes de Mama/efectos adversos , Estradiol , Femenino , Humanos , Mamoplastia/efectos adversos , Ratas , Siliconas , Staphylococcus epidermidis
18.
Am J Hum Genet ; 99(1): 195-201, 2016 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-27321946

RESUMEN

Tooth agenesis is one of the most common developmental anomalies in humans. Oligodontia, a severe form of tooth agenesis, is genetically and phenotypically a heterogeneous condition. Although significant efforts have been made, the genetic etiology of dental agenesis remains largely unknown. In the present study, we performed whole-exome sequencing to identify the causative mutations in Chinese families in whom oligodontia segregates with dominant inheritance. We detected a heterozygous missense mutation (c.632G>A [p.Arg211Gln]) in WNT10B in all affected family members. By Sanger sequencing a cohort of 145 unrelated individuals with non-syndromic oligodontia, we identified three additional mutations (c.569C>G [p.Pro190Arg], c.786G>A [p.Trp262(∗)], and c.851T>G [p.Phe284Cys]). Interestingly, analysis of genotype-phenotype correlations revealed that mutations in WNT10B affect the development of permanent dentition, particularly the lateral incisors. Furthermore, a functional assay demonstrated that each of these mutants could not normally enhance the canonical Wnt signaling in HEPG2 epithelial cells, in which activity of the TOPFlash luciferase reporter was measured. Notably, these mutant WNT10B ligands could not efficiently induce endothelial differentiation of dental pulp stem cells. Our findings provide the identification of autosomal-dominant WNT10B mutations in individuals with oligodontia, which increases the spectrum of congenital tooth agenesis and suggests attenuated Wnt signaling in endothelial differentiation of dental pulp stem cells.


Asunto(s)
Anodoncia/genética , Mutación Missense/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Wnt/genética , Pueblo Asiatico/genética , Secuencia de Bases , China , Pulpa Dental/patología , Exoma/genética , Femenino , Estudios de Asociación Genética , Células Hep G2 , Heterocigoto , Humanos , Masculino , Linaje , Diente/patología , Vía de Señalización Wnt/genética
19.
Environ Sci Technol ; 53(6): 3078-3086, 2019 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-30801184

RESUMEN

Forward osmosis (FO) can potentially treat textile wastewaters with less fouling than pressure-driven membrane processes such as reverse osmosis and nanofiltration. However, conventional FO membranes with asymmetric architecture experience severe flux decline caused by internal concentration polarization and fouling as dye molecules accumulate on the membrane surface. In this study, we present a new strategy for concentrating dye by using a self-standing, support-free FO membrane with a symmetric structure. The membrane was fabricated by a facile solution-casting approach based on a poly(triazole- co-oxadiazole- co-hydrazine) (PTAODH) skeleton. Due to its dense architecture, ultrasmooth surface, and high negative surface charge, the PTAODH membrane exhibits excellent FO performance with minimal fouling, low reverse salt flux, and negligible dye passage to the draw solution side. Cleaning with a 40% alcohol solution, after achieving a concentration factor of ∼10, resulted in high flux recovery ratio (98.7%) for the PTAODH membrane, whereas significant damage to the active layers of two commercial FO membranes was observed. Moreover, due to the existence of cytotoxic oxadiazole and triazole moieties in the polymer structure, our PTAODH membrane exhibited an outstanding antibacterial property with two model bacteria. Our results demonstrate the promising application of the symmetric PTAODH membrane for the concentration of textile wastewaters and its superior antifouling performance compared to state-of-the-art commercial FO membranes.


Asunto(s)
Aguas Residuales , Purificación del Agua , Colorantes , Membranas Artificiales , Ósmosis , Textiles
20.
J Mater Sci Mater Med ; 30(4): 41, 2019 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-30919092

RESUMEN

For cartilage tissue repairing, it remains a key challenge to design implant materials with antibacterial activity, proper degradation rate and mechanical property. In this research, antibacterial nanodiamonds (QND, QND-Ag) modified acrylate-terminated polyurethanes (APU) were prepared. By the addition of nanocomposites, the crystallinity of modified APU obviously increased, which indicates a strong interaction between NDs and APU. Tensile and compression tests were carried out to evaluate the improved mechanical properties. Compared with APU, APU(10%PEG)/QND-Ag possessed the increased modulus and strength, a nevertheless slight decrease in elongation at break. Due to the dual actions of contact-killing of cationic polymers and release-killing of the Ag NPs, QND-Ag-containing polyurethane showed excellent antibacterial activity against Staphylococcus aureus. Moreover, APU containing polyethylene glycol showed a significant increase in degradability rates. Consequently, owing to the dual effect of crystallinity and hydrophilicity, our modified APU exhibited the proper degradation rate adaptable to the healing rate of cartilage tissue. Furthermore, the CCK-8 results demonstrated that synthesized samples were low toxic. Therefore, APU(10%PEG)/QND-Ag holds great promise for the application of cartilage tissue repairing.


Asunto(s)
Antibacterianos , Cartílago , Regeneración Tisular Dirigida , Nanodiamantes/química , Poliuretanos/química , Plata/administración & dosificación , Andamios del Tejido/química , Implantes Absorbibles , Animales , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacología , Fenómenos Biomecánicos , Cartílago/citología , Cartílago/efectos de los fármacos , Cartílago/fisiología , Células Cultivadas , Preparaciones de Acción Retardada , Portadores de Fármacos/química , Regeneración Tisular Dirigida/instrumentación , Regeneración Tisular Dirigida/métodos , Ensayo de Materiales , Ratones , Pruebas de Sensibilidad Microbiana , Poliaminas , Polielectrolitos , Regeneración/efectos de los fármacos , Plata/farmacocinética , Staphylococcus aureus , Estrés Mecánico , Cicatrización de Heridas/efectos de los fármacos
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