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1.
Neurosurg Rev ; 47(1): 520, 2024 Sep 02.
Article de Anglais | MEDLINE | ID: mdl-39222163

RÉSUMÉ

OBJECTIVE: To propose a screw algorithm and investigate the anatomical feasibilities and clinical outcomes of five distinct fixation methods for C2-3 fused vertebra with high-ridding vertebral arteries (VA) (HRVA) when the C2 pedicle screw placement is unfeasible. METHODS: Thirty surgical patients with congenital C2-3 fusion, HRVA, and atlantoaxial dislocation (AAD) were included. We designed a algorithm for alternative screw implantation into C2-3 fused vertebrae, including C2 pedicle screw with in-out-in (passing VA groove) technique (in-out-in screw), subfacetal screw, translaminar screw, lateral mass screw, C3 pedicle screw. VA diameter and position, C2 and C3 pedicles, superior facets, fused lamina, and fused lateral mass dimensions were evaluated for screw implantation indication. Implant failure, reduction loss, implant placement accuracy were investigated by computed tomography. RESULTS: A total of 5 VAs were identified as distant VAs; a total of 2 VAs were categorized as occlusive VAs. Sufficient dimension of lateral mass and lamina provided the broadest indications for screw implantation, while the distant or occlusive VA provided the most limited indications for in-out-in screw. The indications of five alternative methods ranged from narrowest to widest as follows: in-out-in screw, C3 pedicle screw, subfacetal screw, translaminar screw, lateral mass screw. The translaminar screws and the lateral mass screws increased the probability of implant failure. All patients who received in-out-in screws, C3 pedicle screws, and subfacetal screws achieved fusion. The accuracy ranged from lowest to highest as follows: C3 pedicle screw, lateral mass screw, in-out-in screw, subfacetal screw, translaminar screw. No translaminar screws deviated. CONCLUSIONS: The algorithm proved to be a valuable tool for screw selection in cases of C2-3 fused vertebrae with HRVAs. The subfacetal screw, boasting broad indications, a high fusion rate, and exceptional accuracy, stood as the primary preferred alternative.


Sujet(s)
Algorithmes , Vis pédiculaires , Arthrodèse vertébrale , Artère vertébrale , Humains , Mâle , Arthrodèse vertébrale/méthodes , Femelle , Adulte , Artère vertébrale/chirurgie , Adulte d'âge moyen , Résultat thérapeutique , Jeune adulte , Adolescent , Vertèbres cervicales/chirurgie , Articulation atlantoaxoïdienne/chirurgie , Vis orthopédiques , Sujet âgé
2.
JAAD Case Rep ; 50: 148-150, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39171202
3.
BMC Infect Dis ; 24(1): 116, 2024 Jan 22.
Article de Anglais | MEDLINE | ID: mdl-38254025

RÉSUMÉ

OBJECTIVE: This study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE. METHODS: This was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis. RESULTS: This study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P < 0.05). However, there was no significant difference in the distribution of carbapenemase strains or enzymes between the two groups. CONCLUSIONS: The detection rate of CRE was significantly greater in provincial capital hospitals than in nonprovincial capital hospitals. The source of the patients, invasive procedures, and use of advanced antibiotics may account for the differences. Carbapenem-resistant Klebsiella pneumoniae (CR-KPN) was the most prevalent strain. Klebsiella pneumoniae carbapenemase (KPC) was the predominant carbapenemase enzyme. The distributions of carbapenemase strains and enzymes were similar in different regions.


Sujet(s)
Antibactériens , Température du corps , Humains , Études transversales , Antibactériens/pharmacologie , Antibactériens/usage thérapeutique , Canule , Carbapénèmes/pharmacologie , Klebsiella pneumoniae
4.
ACS Nano ; 17(21): 21182-21194, 2023 11 14.
Article de Anglais | MEDLINE | ID: mdl-37901961

RÉSUMÉ

The technology of aggregation-induced emission (AIE) presents a promising avenue for fluorescence imaging-guided photodynamic cancer therapy. However, existing near-infrared AIE photosensitizers (PSs) frequently encounter limitations, including tedious synthesis, poor tumor retention, and a limited understanding of the underlying molecular biology mechanism. Herein, an effective molecular design paradigm of anion-π+ interaction combined with the inherently crowded conformation that could enhance fluorescence efficacy and reactive oxygen species generation was proposed through a concise synthetic method. Mechanistically, upon photosensitization, the Hippo signaling pathway contributes to the death of melanoma cells and promotes the nuclear location of its downstream factor, yes-associated protein, which regulates the transcription and expression of apoptosis-related genes. The finding in this study would trigger the development of high-performance and versatile AIE PSs for precision cancer therapy based on a definite regulatory mechanism.


Sujet(s)
Tumeurs , Photothérapie dynamique , Humains , Voie de signalisation Hippo , Médecine de précision , Tumeurs/traitement médicamenteux , Photothérapie dynamique/méthodes , Photosensibilisants/pharmacologie , Photosensibilisants/usage thérapeutique , Espèces réactives de l'oxygène/métabolisme
5.
Clin Neurol Neurosurg ; 232: 107848, 2023 09.
Article de Anglais | MEDLINE | ID: mdl-37419081

RÉSUMÉ

PURPOSE: In economically undeveloped areas, surgery for basilar invagination (BI) is still a serious economic burden for people. This study introduces a modified interfacet technique for the treatment of BI using shaped autologous occipital bone mass to reduce BI and to save economical expenditure. METHODS: The data of 6 patients with BI who underwent modified interfacet technique using shaped autologous occipital bone mass in our hospital from April 2020 to February 2021 were retrospectively analyzed. During the operation, osteotomy at the external occipital protuberance was performed using ultrasonic osteotome, followed by interfacet release and implantation of shaped autologous occipital bone mass to complete vertical reduction. The atlantodental interval (ADI), Chamberlain's line violation (CLV), clivo-axial angle (CXA) and cervico-medullary angle (CMA) were compared before and after surgery. Additionally, we observed implant stability during the follow-up period to assess the long-term success of the modified interfacet technique. RESULTS: The surgical procedure was successful in all six patients, with no reported incidents of vascular injury, spinal cord injury, or dural tear. Following the operation, improvements were observed in the ADI, CLV, CXA, and CMA. Throughout the follow-up period, the implants remained stable, demonstrating no complications such as bone resorption of the autologous occipital bone mass, implant fracture, or displacement. CONCLUSION: The utilization of shaped autologous occipital bone mass in atlantoaxial interfacet bone grafting has demonstrated effectiveness and feasibility. This technique offers simplicity, ease of preparation, and cost-effectiveness, making it a viable option for treating BI.


Sujet(s)
Articulation atlantoaxoïdienne , Luxations , Platybasie , Arthrodèse vertébrale , Humains , Études rétrospectives , Luxations/chirurgie , Articulation atlantoaxoïdienne/chirurgie , Platybasie/chirurgie , Os occipital/imagerie diagnostique , Os occipital/chirurgie , Arthrodèse vertébrale/méthodes
6.
Phys Chem Chem Phys ; 25(28): 18775-18787, 2023 Jul 19.
Article de Anglais | MEDLINE | ID: mdl-37431672

RÉSUMÉ

To interpret the HeI photoelectron spectrum of Cl2O (involving four lowest electronic states of Cl2O+), in this work we first constructed the associated adiabatic full-dimensional potential energy surfaces (PESs) of Cl2O(X̃1A1), Cl2O+(X̃2B1), and Cl2O+(C̃2A2) and a diabatic potential energy matrix (PEM) of Cl2O+(Ã2B2, B̃2A1, and 22A1) using the explicitly correlated internally contracted multi-reference configurational interaction with Davidson correction (MRCI-F12+Q) and neural network methods. Particularly for the Ã2B2, B̃2A1, and 22A1 states of Cl2O+ coupled in terms of conical intersection, their diabatization is achieved by the neural network approach based merely on the associated adiabatic energies. With the help of newly constructed adiabatic PESs and the diabatic PEM, the HeI photoelectron spectrum of Cl2O is further computed quantum mechanically. The calculated photoelectron spectrum is found to be in good accord with experiment. The mode specificity in the HeI photoelectron bands of Cl2O is analyzed in detail.

7.
World Neurosurg ; 172: 72, 2023 Apr.
Article de Anglais | MEDLINE | ID: mdl-36736772

RÉSUMÉ

Type B basilar invagination (BI) refers to odontoid process prolapse into skull base without dislocation, which is often associated with Chiari malformation and syringomyelia.1 Its pathogenesis and treatment are in controversy. Posterior fossa decompression has been introduced to treat the associated Chiari malformation; however, it may not be effective for symptoms with severe ventral nerve compression.2 C1-2 in situ fixation has been reported to treat minor instability in type B BI,3 yet the assessment of minor instability has not been widely accepted. We believe that the pathogenesis is chronic ventral compression of the brainstem. Transoral odontoidectomy is a classic surgical procedure to treat the pathogenesis, but it is associated with high risks of infection, velopharyngeal incompetence, and airway obstruction and often requires posterior surgery for fusion.4 Thus we use an interfacet distraction technique to move the odontoid process down and relieve ventral brainstem compression.5 Therefore interfacet structural support is necessary to maintain the distance of the interfacet. The reason for fixation is that interfacet distraction disrupts atlantoaxial stability. We designed a novel sliding-traction head holder, which can quantitatively tract and stabilize the head without support for the head or face, avoiding the risk of eyeball compression. It adapts to a variety of surgical methods and allows intraoperative changes in the patient's position. Assisted by the device, a satisfied interfacet distraction and a correction of BI were obtained. Video 1 describes how the interfacet distraction technique assisted by a sliding-traction head holder was performed in an illustrative case. The patient consented to the procedure.


Sujet(s)
Malformation d'Arnold-Chiari , Articulation atlantoaxoïdienne , Luxations , Platybasie , Arthrodèse vertébrale , Humains , Traction , Platybasie/chirurgie , Malformation d'Arnold-Chiari/imagerie diagnostique , Malformation d'Arnold-Chiari/chirurgie , Malformation d'Arnold-Chiari/complications , Luxations/chirurgie , Décompression chirurgicale/méthodes , Arthrodèse vertébrale/méthodes , Articulation atlantoaxoïdienne/chirurgie
8.
Article de Anglais | MEDLINE | ID: mdl-36473299

RÉSUMÉ

OBJECTIVE: The aim of this study is to develop a LC-MS/MS method for the quantitation of seven cytochrome P450 (CYP450) enzymes. METHODS: A high-performance liquid chromatography-tandem mass spectrometry method was developed using multiple reaction monitoring mode with positive electrospray ionization. The method was validated with selectivity, linearity, stability, accuracy and precious. In addition, the abundance of seven CYP450 enzymes in human liver microsomes and CYP3A4 in placenta were determined using the current method. RESULTS: The linear range for CYP1A2, CYP2B6 and CYP2C8 was 0.036-3.6 nM and for CYP2C9, CYP2C19, CYP2D6 and CYP3A4 was 0.090-9.0 nM. No interference was found between the blank matrix and each specific peptides. The accuracy and precious results were in accord with the requirement of analytical methods for biological samples in Chinese Pharmacopoeia. In addition, the peptides were stable under current stability conditions. The content of CYP3A4 in placenta and the seven CYP450 enzymes in human liver microsomes were accurately quantified. CONCLUSION: The developed method is sensitive and specific and can be applied to the quantification of enzymes abundance in different human derived samples like placenta and liver microsomes.


Sujet(s)
Cytochrome P-450 CYP3A , Spectrométrie de masse en tandem , Humains , Chromatographie en phase liquide/méthodes , Spectrométrie de masse en tandem/méthodes , Cytochrome P-450 CYP3A/métabolisme , Microsomes du foie/métabolisme , Cytochrome P-450 enzyme system/métabolisme
9.
BMC Musculoskelet Disord ; 23(1): 1138, 2022 Dec 29.
Article de Anglais | MEDLINE | ID: mdl-36581884

RÉSUMÉ

BACKGROUND: This study reports on the surgical technique used and clinical outcomes obtained during the treatment of basilar invagination (BI) without atlantoaxial dislocation (AAD) through the correction of the clivus canal angle (CCA) using interfacet distraction and fixation. METHODS: Nineteen cases with BI without AAD treated by the correction of the clivus canal angle were retrospectively analyzed. Pre- and postoperative computed tomography scans and three-dimensional reconstruction views were obtained to measure the size of the CCA, pB-C2 distance, and degree of BI. Chiari malformation and syringomyelia were evaluated by magnetic resonance imaging (MRI). The clinical outcomes for all patients were measured using the Japanese Orthopedic Association (JOA) scale. The CCA was corrected by using interfacet distraction and fixation techniques. The Wilcoxon test was used to compare pre- and postoperative measurements. RESULTS: All the patients were followed up for 24.95 ± 5.22 months (range 12-36 months); no patient suffered intraoperative nerve or vascular injury. Clinical symptoms improved in 17 patients (89.5%). The mean JOA score increased from 12.32 ± 1.89 to 14.37 ± 1.30 (Z = -3.655, P < 0.001). The mean CCA improved from 129.34 ± 8.52° preoperatively to 139.75 ± 8.86° postoperatively (Z = -3.824, P < 0.001). The mean pB-C2 decreased from 7.47 ± 2.21 to 5.68 ± 3.13 (Z = -3.060, P = 0.002). Syringomyelia was significantly reduced in 10 out of 13 patients by the first follow-up year. All patients achieved bony fusion. CONCLUSION: Posterior interfacet distraction and fixation to correct the CCA is a feasible and effective method for treating BI without AAD.


Sujet(s)
Articulation atlantoaxoïdienne , Luxations , Arthrodèse vertébrale , Syringomyélie , Humains , Études rétrospectives , Syringomyélie/imagerie diagnostique , Syringomyélie/chirurgie , Syringomyélie/complications , Articulation atlantoaxoïdienne/imagerie diagnostique , Articulation atlantoaxoïdienne/chirurgie , Articulation atlantoaxoïdienne/traumatismes , Luxations/imagerie diagnostique , Luxations/chirurgie , Luxations/complications , Décompression chirurgicale/méthodes , Arthrodèse vertébrale/méthodes
10.
Front Pharmacol ; 13: 1065130, 2022.
Article de Anglais | MEDLINE | ID: mdl-36582520

RÉSUMÉ

Olverembatinib (HQP1351) is a third-generation BCR-ABL tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia (CML) (including T315I-mutant disease), exhibits drug-drug interaction (DDI) potential through cytochrome P450 (CYP) enzymes CYP3A4, CYP2C9, CYP2C19, CYP1A2, and CYP2B6. A physiologically-based pharmacokinetic (PBPK) model was constructed based on physicochemical and in vitro parameters, as well as clinical data to predict 1) potential DDIs between olverembatinib and CYP3A4 and CYP2C9 inhibitors or inducers 2), effects of olverembatinib on the exposure of CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 substrates, and 3) pharmacokinetics in patients with liver function injury. The PBPK model successfully described observed plasma concentrations of olverembatinib from healthy subjects and patients with CML after a single administration, and predicted olverembatinib exposure increases when co-administered with itraconazole (strong CYP3A4 inhibitor) and decreases with rifampicin (strong CYP3A4 inducer), which were validated by observed data. The predicted results suggest that 1) strong, moderate, and mild CYP3A4 inhibitors (which have some overlap with CYP2C9 inhibitors) may increase olverembatinib exposure by approximately 2.39-, 1.80- to 2.39-, and 1.08-fold, respectively; strong, and moderate CYP3A4 inducers may decrease olverembatinib exposure by approximately 0.29-, and 0.35- to 0.56-fold, respectively 2); olverembatinib, as a "perpetrator," would have no or limited impact on CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 enzyme activity 3); systemic exposure of olverembatinib in liver function injury with Child-Pugh A, B, C may increase by 1.22-, 1.79-, and 2.13-fold, respectively. These simulations inform DDI risk for olverembatinib as either a "victim" or "perpetrator".

11.
J Orthop Surg Res ; 17(1): 495, 2022 Nov 16.
Article de Anglais | MEDLINE | ID: mdl-36384627

RÉSUMÉ

OBJECTIVE: This study aims to investigate the clinical application and feasibility of C2 subfacetal screws in patients with Klippel-Feil syndrome (KFS), narrow C2 pedicles, and high-riding vertebral arteries (HRVAs). METHODS: The clinical data of seven patients with KFS, atlantoaxial dislocation, narrow C2 pedicles, and HRVAs treated with C2 subfacetal screws were analyzed in this retrospective study. The internal height, isthmus height, and pedicle width of C2 vertebra were measured using preoperative computed tomography (CT). Subfacetal screws were inserted for 7 patients (12 sides). The position and length of the screws were observed using postoperative CT. Intraoperative dura mater and vertebral artery (VA) injuries were recorded. Bone fusion was observed using follow-up CT. RESULTS: The internal height was 10.5 ± 3.2 mm, the isthmus height was 3.7 ± 1.8 mm, the pedicle width was 3.0 ± 1.4 mm, and the screw length was 19.7 ± 1.5 mm. All patients had HRVAs and narrow pedicles. No injury to the dura mater and vertebral artery (VA) occurred in this group of patients. Bone fusion was achieved in all patients during follow-up. CONCLUSIONS: In patients with KFS, HRVA, and a narrow C2 pedicle, there is sufficient space below the C2 articular surface for screw insertion. When the pedicle is narrow and the C2 pedicle screw is not suitable for placement due to possible injury to the VA, subfacetal screws are a feasible alternative.


Sujet(s)
Luxations , Syndrome de Klippel-Feil , Vis pédiculaires , Arthrodèse vertébrale , Humains , Artère vertébrale/imagerie diagnostique , Artère vertébrale/chirurgie , Artère vertébrale/traumatismes , Syndrome de Klippel-Feil/complications , Syndrome de Klippel-Feil/imagerie diagnostique , Syndrome de Klippel-Feil/chirurgie , Études rétrospectives , Arthrodèse vertébrale/méthodes , Luxations/imagerie diagnostique , Luxations/chirurgie
12.
Front Genet ; 13: 1011676, 2022.
Article de Anglais | MEDLINE | ID: mdl-36267407

RÉSUMÉ

Davidia involucrata is a significant living fossil with high abiotic stress tolerance. Although heat shock protein 20 (HSP20) has already been linked to heat stress, nothing is known about HSP20 family protein activities in D. involucrata. The functional dynamics of the D. involucrata HSP20 (DiHSP20) gene family were identified and characterized using a thorough genome-wide investigation. From the genome of D. involucrata, a total of 42 HSP20 genes were identified, which are distributed across 16 chromosomes. The DiHSP20 proteins were grouped into seven separate subfamilies by our phylogenetic analysis, which was validated by the conserved motif composition and gene structure studies. Segmental duplication events were shown to play a crucial role in the expansion of the DiHSP20 gene family. Synteny analysis revealed that 19 DiHSP20 genes of D. involucrata shared a syntenic connection with Arabidopsis genes, 39 with C. acuminata genes, and just 6 with O. sativa genes. Additionally, heat stress differently enhanced the expression levels of D. involucrata HSP20 genes. After 1 hour of heat treatment, the expression levels of most DiHSP20 genes, particularly DiHSP20-7, DiHSP20-29, DiHSP20-30, DiHSP20-32, and DiHSP20-34, were dramatically increased, suggestted that they might be employed as heat tolerance candidate genes. Overall, these findings add to our knowledge of the HSP20 family genes and provide helpful information for breeding heat stress resistance in D. involucrata.

13.
Article de Anglais | MEDLINE | ID: mdl-36011827

RÉSUMÉ

This study explored the configuration effect of human capital, social capital, and psychological capital on employee well-being. A total of 458 employees were investigated via a human capital scale, social capital scale, Chinese psychological capital scale, and multiple well-being questionnaire. The result of the fuzzy-set qualitative comparative analysis showed that human capital, social capital, and psychological capital in the form of diversified configuration will achieve high well-being, characterized by "all roads lead to Rome". Even without human capital and social capital, high well-being can be achieved as long as psychological capital exists. Psychological capital is the most critical factor affecting subjective well-being, followed by human capital and social capital. Compared with guanxi-oriented psychological capital, task-oriented psychological capital is a more critical factor in achieving high well-being.


Sujet(s)
Capital social , Humains , Enquêtes et questionnaires
14.
Front Psychol ; 13: 938875, 2022.
Article de Anglais | MEDLINE | ID: mdl-36033065

RÉSUMÉ

The present study investigated the configuration effect of human capital, social capital, and psychological capital on job performance. The human capital questionnaire, social capital scale, psychological capital scale, and job performance scale were used to survey 458 employees. Results revealed that four antecedent configurations could achieve high task performance, and three antecedent configurations can achieve high contextual performance. The high job performance driving path was characterized by "all roads lead to Rome." Human capital, social capital, and psychological capital affected job performance in the form of configuration, which reflected the asymmetric causal relationship.

15.
Front Plant Sci ; 13: 911467, 2022.
Article de Anglais | MEDLINE | ID: mdl-35747877

RÉSUMÉ

Populus alba (P. alba) and Populus davidiana (P. davidiana) are important plant species for answering a variety of issues on species evolution due to their wide distribution and ability to adapt to a variety of environments and climates. Even though P. alba and P. davidiana belong to ecologically and economically important forest trees in the Northern Hemisphere, little is known about their genomic landscape and genome divergence during speciation. We re-sequenced 20 and 19 members of P. davidiana and P. alba, respectively, and found that the Dxy value between P. alba and P. davidiana was 0.2658, whereas the F ST values were 0.2988, indicating that the genetic divergence was fairly clear. Populus davidiana and P. alba diverged from the ancestor in the middle Pleistocene, c. 0.80 Ma (95% HPD: 0.79-0.81 Ma). The population sizes of P. davidiana increased ~20,000 years ago after a considerable long-term decline following divergence. However, after differentiation, the effective population size of P. alba expanded slightly before experiencing a long-term bottleneck effect. According to the expectation of allopatric speciation, we found a significant number of genomic differentiation sites in both species' speciation events, and the majority of these genomic differentiation regions can be attributed to neutral evolutionary processes. Nevertheless, the regions with extreme divergence exist in abundance, indicating that natural selection has had an impact. Positive selection can be found in highly differentiated regions, while long-term balancing selection traits can be easily observed in low differentiated regions. According to these findings, climate differences over the Quaternary, as well as variance in linked selection and recombination, all contributed significantly to genomic divergence during allopatric speciation of the two aspens.

16.
Acta Psychol (Amst) ; 227: 103612, 2022 Jul.
Article de Anglais | MEDLINE | ID: mdl-35598380

RÉSUMÉ

The COVID-19 pandemic has brought unprecedented challenges for adolescents, who tended to experience more emotional instability, impulsivity, and aggressive behavior driven by the fear of infection and the uncertainty of network information. In the present study, we investigated the relationship between Internet addiction and aggressive behavior, and the mediating effects of depression and anxiety. There were differences in Internete addiction and aggressive behavior in gender, thus the moderating role of gender between them were explored. A total of 1148 middle school students were invited to complete the Buss Perry Aggression Questionnaire, the Internet Addition Scale, the Self-rating Depression Scale (SDS), and the Self-rating Anxiety Scale (SAS) separately. The results suggested that 1) there was a significant positive correlation between Internet addiction and aggressive behavior; 2) anxiety, but not depression, mediated the effect of Internet addiction on aggressive behavior; 3) gender did not moderate the effect of Internet addiction on aggressive behavior. The practical implication of the current findings on boosting adolescents' mental health was discussed and further suggestions were provided.


Sujet(s)
COVID-19 , Dépendance à Internet , Adolescent , Agressivité/psychologie , Anxiété/épidémiologie , Anxiété/psychologie , COVID-19/épidémiologie , Dépression/épidémiologie , Dépression/psychologie , Humains , Internet , Dépendance à Internet/épidémiologie , Pandémies
17.
Regen Biomater ; 9: rbac002, 2022.
Article de Anglais | MEDLINE | ID: mdl-35480861

RÉSUMÉ

Magnesium alloy (Mg alloy) has attracted massive attention in the potential applications of cardiovascular stents because of its good biocompatibility and degradability. However, whether and how the Mg alloy induces inflammation in endothelial cells remains unclear. In the present work, we investigated the activation of Yes-associated protein (YAP) upon Mg alloy stimuli and unveiled the transcriptional function in Mg alloy-induced inflammation. Quantitative RT-PCR, western blotting and immunofluorescence staining showed that Mg alloy inhibited the Hippo pathway to facilitate nuclear shuttling and activation of YAP in human coronary artery endothelial cells (HCAECs). Chromatin immunoprecipitation followed sequencing was carried out to explore the transcriptional function of YAP in Mg alloy-derived inflammation. This led to the observation that nuclear YAP further bonded to the promoter region of inflammation transcription factors and co-transcription factors. This binding event activated their transcription and modified mRNA methylation of inflammation-related genes through regulating the expression of N6-methyladenosine modulators (METTL3, METTL14, FTO and WTAP). This then promoted inflammation-related gene expression and aggravated inflammation in HCAECs. In YAP deficiency cells, Mg alloy-induced inflammation was reduced. Collectively, our data suggest that YAP contributes to the Mg alloy-derived inflammation in HCAECs and may provide a potential therapeutic target that alleviates inflammation after Mg alloy stent implantation.

18.
Biochim Biophys Acta Mol Cell Res ; 1869(4): 119211, 2022 04.
Article de Anglais | MEDLINE | ID: mdl-35041860

RÉSUMÉ

Inhibition of vascular smooth muscle cells (VSMCs) proliferation without dysregulating endothelial cells (ECs) may provide an ideal therapy for in-stent restenosis. Due to its anti-proliferation effect on VSMCs and pro-endothelium effect, arsenic trioxide (ATO) has been used in a drug-eluting stent in a recent clinical trial. However, the underlying mechanism by which ATO achieves this effect has not been determined. In the present work, we showed that ATO induced apoptosis in VSMCs but not in ECs. Mechanistically, ATO achieved this through modulation of cellular metabolism to increase lysophosphatidic acid (LPA) in VSMCs, while LPA concentration was stable in ECs. The elevated LPA facilitated the nuclear accumulation and initiated the transcriptional function of Yes-associated protein (YAP) in VSMCs. YAP regulated the transcription of N6-Methyladenosine (m6A) modulators (Mettl14 and Wtap) to increase the m6A methylation levels of apoptosis-related genes to induce their high expression and exacerbate VSMCs apoptosis. On the other hand, YAP nuclear accumulation in ECs was not observed. Collectively, our data exhibited the molecular process involved in selective apoptosis of VSMCs induced by ATO.


Sujet(s)
Apoptose/effets des médicaments et des substances chimiques , Trioxyde d'arsenic/pharmacologie , Protéines du cycle cellulaire/métabolisme , Lysophospholipides/métabolisme , Facteurs de transcription/métabolisme , Animaux , Trioxyde d'arsenic/composition chimique , Inhibiteurs des caspases/pharmacologie , Caspases/composition chimique , Caspases/métabolisme , Protéines du cycle cellulaire/génétique , Lignée cellulaire , Mouvement cellulaire/effets des médicaments et des substances chimiques , Prolifération cellulaire/effets des médicaments et des substances chimiques , Humains , Souris , Souris de lignée C57BL , Muscles lisses vasculaires/cytologie , Muscles lisses vasculaires/métabolisme , Nanoparticules/composition chimique , Facteurs de transcription/génétique
19.
Regen Biomater ; 8(3): rbab017, 2021 Jun.
Article de Anglais | MEDLINE | ID: mdl-34211729

RÉSUMÉ

Due to its good biocompatibility and degradability, magnesium alloy (Mg alloy) has shown great promise in cardiovascular stent applications. Rapid stent re-endothelialization is derived from migrated and adhered endothelial cells (ECs), which is an effective way to reduce late thrombosis and inhibit hyperplasia. However, fundamental questions regarding Mg alloy affecting migration and adhesion of ECs are not fully understood. Here, we evaluated the effects of Mg alloy on the ECs proliferation, adhesion and migration. A global gene expression profiling of ECs co-culturing with Mg alloy was conducted, and the adhesion- and migration-related genes were examined. We found that Mg alloy had no adverse effects on ECs viability but significantly affected ECs migration and adhesion. Co-cultured with Mg alloy extract, ECs showed contractive adhesion morphology and decreased motility, which was supported by the down-regulation of adhesion-related genes (Paxillin and Vinculin) and migration-related genes (RAC 1, Rho A and CDC 42). Accordingly, the re-endothelialization of Mg alloy stent was inhibited in vivo. Our results may provide new inspiration for improving the broad application of Mg alloy stents.

20.
Front Pharmacol ; 12: 648697, 2021.
Article de Anglais | MEDLINE | ID: mdl-34045960

RÉSUMÉ

Background: Physiologically based pharmacokinetic (PBPK) modeling and simulating may be a powerful tool in predicting drug behaviors in specific populations. It is a mathematical model that relates the pharmacokinetic (PK) profile of a compound with human anatomical characteristics, physiological characteristics, and biochemical parameters. Predictions using PBPK models offer a promising way to guide drug development and can be used to optimize clinical dosing regimens. However, PK data of new drugs in the pediatric population are too limited to guide clinical therapy, which may lead to frequent adverse events or insufficient efficacy for pediatric patients, particularly in neonates and infants. Objective: The objective of this study was to establish a virtual Chinese pediatric population based on the physiological parameters of Chinese children that could be utilized in PBPK models. Methods: A Chinese pediatric PBPK model was developed in Simcyp Simulator by collecting published Chinese pediatric physiological and anthropometric data to use as system parameters. This pediatric population model was then evaluated in the Chinese pediatric population by predicting the pharmacokinetic characteristics of four probe drugs: theophylline (major CYP1A2 substrate), fentanyl (major CYP3A4 substrate), vancomycin, and ceftazidime (renal-eliminated). Results: The predicted maximum concentration (Cmax), area under the curve of concentration-time (AUC), and clearance (CL) for theophylline (CYP1A2 metabolism pathway) and fentanyl (CYP3A4 metabolism pathway) were within two folds of the observed data. For drugs mainly eliminated by renal clearance (vancomycin and ceftazidime) in the Chinese pediatric population, the ratio of prediction to observation for major PK parameters was within a 2-fold error range. Conclusion: The model is a supplement to the previous Chinese population PBPK model. We anticipate the model to be a better representative of the pediatric Chinese population for drugs PK, offering greater clinical precision for medication given to the pediatric population, ultimately advancing clinical development of pediatric drugs. We can refine this model further by collecting more physiological parameters of Chinese children.

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