Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.151
Filtrar
1.
Exp Cell Res ; : 113026, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35026284

RESUMO

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are well-established as vital regulators of fracture healing, whereas angiogenesis is one of the critical processes during the course of bone healing. Accordingly, the current study sought to determine the functions of microRNA (miR)-29b-3p from BM-MSCs-derived extracellular vesicles (EVs) on the angiogenesis of fracture healing via the PTEN/PI3K/AKT axis. Firstly, BM-MSCs-EVs were extracted and identified. The lentiviral protocol was adopted to construct miR-29b-3pKD-BMSCs or miR-negative control-BMSCs, which were then co-cultured with human umbilical vein endothelial cells (HUVECs) in vitro to determine the roles of EVs-encapsulated miR-29b-3p on the proliferation, migration, and angiogenesis of HUVECs in vitro with the help of a CCK-8 assay, scratch test, and tube formation assay. Subsequent database prediction, luciferase activity assay, RT-qPCR, and Western blot assay findings identified the downstream target gene of miR-29b-3p, PTEN, and a signaling pathway, PI3K/AKT. Furthermore, the application of si-PTEN attenuated the effects induced by miR-29b-3pKD-EVs. Finally, a mouse model of femoral fracture was established with a locally instilled injection of equal volumes of BM-MSCs-EVs and miR-29b-3pKD-BM-MSCs-EVs. Notably, the mice treated with BMSC-EVs presented with enhanced neovascularization at the fracture site, in addition to increased bone volume (BV), BV/tissue volume, and mean bone mineral density; whereas miR-29b-3pKD-BMSCs-EVs-treated mice exhibited decreased vessel density with poor fracture healing capacity. Collectively, our findings elicited that BM-MSCs-EVs carrying miR-29b-3p were endocytosed by HUVECs, which consequently suppressed the PTEN expression and activated the PI3K/AKT pathway, thereby promoting HUVEC proliferation, migration, and angiogenesis, and ultimately facilitating fracture healing.

2.
Neural Regen Res ; 17(8): 1685-1694, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35017415

RESUMO

In 2001, the concept of the neurovascular unit was introduced at the Stroke Progress Review Group meeting. The neurovascular unit is an important element of the health and disease status of blood vessels and nerves in the central nervous system. Since then, the neurovascular unit has attracted increasing interest from research teams, who have contributed greatly to the prevention, treatment, and prognosis of stroke and neurodegenerative diseases. However, additional research is needed to establish an efficient, low-cost, and low-energy in vitro model of the neurovascular unit, as well as enable noninvasive observation of neurovascular units in vivo and in vitro. In this review, we first summarize the composition of neurovascular units, then investigate the efficacy of different types of stem cells and cell culture methods in the construction of neurovascular unit models, and finally assess the progress of imaging methods used to observe neurovascular units in recent years and their positive role in the monitoring and investigation of the mechanisms of a variety of central nervous system diseases.

3.
JAMA Neurol ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34982098

RESUMO

Importance: In-stent restenosis (ISR) is the primary reason for stroke recurrence after intracranial stenting in patients who were treated with a standard bare-metal stent (BMS). Whether a drug-eluting stent (DES) could reduce the risk of ISR in intracranial atherosclerotic stenosis (ICAS) remains unclear. Objective: To investigate whether a DES can reduce the risk of ISR and stroke recurrence in patients with symptomatic high-grade ICAS. Design, Settings, and Participants: A prospective, multicenter, open-label randomized clinical trial with blinded outcome assessment was conducted from April 27, 2015, to November 16, 2018, at 16 medical centers in China with a high volume of intracranial stenting. Patients with symptomatic high-grade ICAS were enrolled, randomized, and followed up for 1 year. Intention-to-treat data analysis was performed from April 1 to May 22, 2021. Interventions: Patients were randomly assigned to receive DES (NOVA intracranial sirolimus-eluting stent system) or BMS (Apollo intracranial stent system) treatment in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy end point was ISR within 1 year after the procedure, which was defined as stenosis that was greater than 50% of the luminal diameter within or immediately adjacent to (within 5 mm) the implanted stent. The primary safety end point was any stroke or death within 30 days after the procedure. Results: A total of 263 participants (194 men [73.8%]; median [IQR] age, 58 [52-65] years) were included in the analysis, with 132 participants randomly assigned to the DES group and 131 to the BMS group. The 1-year ISR rate was lower in the DES group than in the BMS group (10 [9.5%] vs 32 [30.2%]; odds ratio, 0.24; 95% CI, 0.11-0.52; P < .001). The DES group also had a significantly lower ischemic stroke recurrence rate from day 31 to 1 year (1 [0.8%] vs 9 [6.9%]; hazard ratio, 0.10; 95% CI, 0.01-0.80; P = .03). No significant difference in the rate of any stroke or death within 30 days was observed between the DES and BMS groups (10 [7.6%] vs 7 [5.3%]; odds ratio, 1.45; 95% CI, 0.54-3.94; P = .46). Conclusions and Relevance: This trial found that, compared with BMSs, DESs reduced the risks of ISR and ischemic stroke recurrence in patients with symptomatic high-grade ICAS. Further investigation into the safety and efficacy of DESs is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02578069.

4.
Carbohydr Polym ; 278: 118935, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973753

RESUMO

It is an urgent task to exploit effective antimicrobial agents due to the rise of drug-resistant pathogens. Herein, antimicrobial quaternized chitosan/Ag composite nanogels (QCS/Ag CNGs) with tunable properties were fabricated through inverse miniemulsion technique with a high encapsulation efficiency of NH2-Ag nanoparticles (NPs). The QCS/Ag CNGs possess superior broad-spectrum antimicrobial activity and low biotoxicity, via synergistic sterilization of Ag NPs and QCS. Furthermore, the NH2-Ag NPs were chemically linked to the QCS matrix through Schiff base reactions, and the QCS/Ag CNGs have reactive groups, making it possible to obtain durable antibacterial cotton fabrics. Thus, QCS/Ag CNGs modified cotton fabrics exhibited laundering durability of antimicrobial effect after 100 washing cycles without sacrificing other inherent properties of cotton fabrics. Our study provides a facile and controllable method to construct polymer/inorganic CNGs to address the urgent need for antibacterial agents/fabrics.

5.
Emerg Microbes Infect ; : 1-9, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34983331

RESUMO

Since the SARS-CoV-2 Omicron variant was first reported from South Africa, it has rapidly spread in over 100 countries. Only two cases infected by the Omicron variant were recently identified in China. The one case in Guangzhou has a relatively long incubation time and mild symptoms. Analysis of the complete viral genome sequence shows three missing Omicron unique mutations and one additional mutation in the newly characterized genome. These unique mutations may be related to the clinical presentation in this case.

6.
Paediatr Anaesth ; 2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35066973

RESUMO

BACKGROUND: Concern for a role of anesthesia in neurotoxicity in children originated from neonatal rodent and non-human primate (NHP) models, yet prospective clinical studies have largely not supported this concern. The goal of this study was to conduct an objective assessment of published NHP study rigor in design, execution, and reporting. METHODS: A MEDLINE search from 2005 to December 2021 was performed. Inclusion criteria included full-length original studies published in English under peer-reviewed journals. We documented experimental parameters on anesthetic dosing, monitoring, vitals, and experimental outcomes. RESULTS: Twenty-three manuscripts were included. Critical issues identified in study design included: lack of blinding in data acquisition (57%) and analysis (100%), supratherapeutic (4-12 fold) maintenance dosing in 22% of studies, lack of sample size justification (91%) resulting in a mean (SD) sample size of 6 (3) animals per group. Critical items identified in the conduct and reporting of studies included: documentation of anesthesia provider (0%), electrocardiogram monitoring (35%), arterial monitoring (4%), spontaneous ventilation employed (35%), failed intubations resulting in comingling ventilated and unventilated animals in data analysis, inaccurate reporting of failed intubation, and only 50% reporting on survival. Inconsistencies were noted in drug related induction of neuroapoptosis and region of occurrence. Further, 67-100% of behavior outcomes were not significantly different from controls. CONCLUSIONS: Important deficits in study design, execution, and reporting were identified in neonatal NHP studies. These results raise concern for the validity and reliability of these studies and may explain in part the divergence from results obtained in human neonates.

7.
Lipids Health Dis ; 21(1): 13, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35057794

RESUMO

BACKGROUND: Benzo [a] pyrene (BaP), a potent carcinogen, has been proved that it has toxicological effects via activation the aryl hydrocarbon receptor (AhR) pathway. AhR can participate in regulating lipogenesis and lipolysis. This topic will verify whether BaP regulates lipid metabolism via AhR. METHODS: (1) C57BL/6 mice were gavaged with BaP for 12 weeks to detect serum lipids, glucose tolerance, and insulin resistance. Morphological changes in white adipose tissue (WAT) were detected by Hematoxylin and Eosin staining. The mRNA expression levels of adipogenesis-related factors included recombinant human CCAAT/enhancer binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), and fatty acid binding protein 4 (FABP4) and inflammatory factors included nuclear factor kappa-B (NF-κB), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α) were detected using PCR. (2) Neutral lipid content changes in differentiated 3 T3-L1 adipocytes treated with BaP with and w/o AhR inhibitor were detected by Oil red staining. The protein expression levels of adipogenesis- and decomposition-related factors included PPARγ coactivator-1 alpha (PGC-1α), and peroxisome proliferation-activated receptor alpha (PPARα) were detected using western blotting. The mRNA expression levels of inflammatory factors were detected using PCR. RESULTS: (1) BaP inhibited body weight gain, decreased lipid content, increased lipid levels, and decreased glucose tolerance and insulin tolerance in mice; (2) BaP reduced the expressions of C/EBPα, PPARγ, FABP4, PGC-1α, and PPARα and increased the expressions of NF-κB, MCP-1, and TNF-α by activating AhR. CONCLUSION: BaP inhibit fat synthesis and oxidation while inducing inflammation by activating AhR, leading to WAT dysfunction and causing metabolic complications.

8.
Adv Mater ; : e2109920, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35060673

RESUMO

XXXX This article is protected by copyright. All rights reserved.

9.
Nucleic Acids Res ; 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35061906

RESUMO

Given the fact that the localization of RNAs is closely associated with their functions, techniques developed for tracking the distribution of RNAs in live cells have greatly advanced the study of RNA biology. Recently, innovative application of fluorescent protein-labelled Cas9 and Cas13 into live-cell RNA tracking further enriches the toolbox. However, the Cas9/Cas13 platform, as well as the widely-used MS2-MCP technique, failed to solve the problem of high background noise. It was recently reported that CRISPR/Cas6 would exhibit allosteric alteration after interacting with the Cas6 binding site (CBS) on RNAs. Here, we exploited this feature and designed a Cas6-based switch platform for detecting target RNAs in vivo. Conjugating split-Venus fragments to both ends of the endoribonuclease-mutated Escherichia coli Cas6(dEcCas6) allowed ligand (CBS)-activated split-Venus complementation. We name this platform as Cas6 based Fluorescence Complementation (Cas6FC). In living cells, Cas6FC could detect target RNAs with nearly free background noise. Moreover, as minimal as one copy of CBS (29nt) tagged in an RNA of interest was able to turn on Cas6FC fluorescence, which greatly reduced the odds of potential alteration of conformation and localization of target RNAs. Thus, we developed a new RNA tracking platform inherently with high sensitivity and specificity.

10.
Gene ; 816: 146172, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34995734

RESUMO

OBJECTIVE: Synovial sarcoma (SS) is a malignant soft tissue sarcoma and its natural history is a long, indolent clinical course followed by high rate of local recurrence and distant metastasis. Current therapies are still limited in increasing satisfactory of 5-year survival, especially for patients with recurrence and metastasis. Accordingly, finding new therapeutic drug for SS treatment is clinically urgent need. Diallyl trisulfide (DATS), a bioactive compound derived from garlic, is reported as a promising anti-cancer agent for various carcinomas. However, its effect on anti-SS remains unknown. This study investigated the anti-SS effect of DATS in human synovial sarcoma SW982 cells. METHODS: CCK-8 assay were used to examine the cell viability. High-content Imaging System was used to examine the apoptosis, intracellular ROS and autophagy. Flow cytometry was used to detect cell cycle. qPCR and Western blot were used to examine the expression of related mRNA and protein. High-throughput RNA-sequencing and bio-information analysis were used to investigate the mRNA profiling. RESULTS: The results showed a suppressive effect of DATS on tumor biology of SW982 cells including inducing apoptosis, triggering G2/M cell cycle arrest, elevating intracellular ROS and damaging mitochondria. Further high-throughput RNA-sequencing analysis clarified a comprehensive molecular portrait for DATS-induced transcriptional regulation. Besides, protein-protein interaction (PPI) analysis demonstrated that a network consisted of FOXM1, CCNA2, CCNB1, MYBL2, PLK1 and CDK1 might be response for DATS-induced G2/M cell cycle arrest and increased intracellular ROS. Notably, protein feature analysis revealed structure enrichment in microtubule network like kinesin motors domain, and tubulin domain. Molecular function analysis suggested that DATS-induced dysfunction of microtubule network might be the major cause for its effect on cell cycle arrest and successive apoptosis. Furthermore, 28 hub genes (including KIF2C, PLK1, CDK1, BIRC5, CCNB2, CENPF, TPX2, TOP2A and so on) were determined. Finally, pathway analysis showed that DATS-induced differentially expressed genes were mainly involved in cell cycle. CONCLUSION: Collectively, our findings for the first time provided the DATS-induced cellular response and transcriptional profiling of SW982 cells, which proposes that suppression of DATS on SS is multi-targeted and represent a therapeutic evidence for SS.

11.
Comp Biochem Physiol B Biochem Mol Biol ; 259: 110716, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34999221

RESUMO

Vasa gene encodes a protein member of DEAD-box superfamily of ATP-dependent RNA helicases, which plays a key role in germline development in metazoans. In present study, we identified a new germline-specific marker Mrvasa in the prawn Macrobrachium rosenbergii, whose genomic DNA sequence consists of 14 exons and 13 introns. A 2516 bp of full-length Mrvasa cDNA encodes a protein of 603 amino acids. It contains nine conserved motifs, a zinc-finger motif, and RGG repeats. RT-PCR indicated that Mrvasa mRNA was specifically expressed in gonads. QPCR analysis further revealed that the expression of Mrvasa mRNA is much higher in testis than in ovary. In testis, the relative expression level of Mrvasa mRNA in late developing stage is significantly higher than that in early-middle developing stage. During ovarian development, no significant difference in expression was found. In situ hybridization demonstrated that Mrvasa mRNA was localized in germline cells including spermatogonia, spermatocytes, and spermatozoa in testes, and previtellogenic and vitellogenic oocytes in ovary. We then isolated the Mrvasa promoter and determined the transcription core region of this promoter. This is the first report on identification of vasa core promoter in crustaceans. Our results will provide a useful germline-specific marker Mrvasa for tracing germline cell formation and development in M. rosenbergii.

12.
J Neurointerv Surg ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022299

RESUMO

BACKGROUND: Parenchymal hemorrhage (PH) is a troublesome complication after endovascular treatment (EVT). OBJECTIVE: To investigate the incidence, independent predictors, and clinical impact of PH after EVT in patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO). METHODS: Subjects were selected from the ANGEL-ACT Registry. PH was diagnosed according to the European Collaborative Acute Stroke Study classification. Logistic regression analyses were performed to determine the independent predictors of PH, as well as the association between PH and 90-day functional outcome assessed by modified Rankin Scale (mRS) score. RESULTS: Of the 1227 enrolled patients, 147 (12.0%) were diagnosed with PH within 12-36 hours after EVT. On multivariable analysis, low admission Alberta Stroke Program Early CT score (ASPECTS)(adjusted OR (aOR)=1.13, 95% CI 1.02 to 1.26, p=0.020), serum glucose >7 mmol/L (aOR=1.82, 95% CI 1.16 to 2.84, p=0.009), and neutrophil-to-lymphocyte ratio (NLR; aOR=1.05, 95% CI 1.02 to 1.09, p=0.005) were associated with a high risk of PH, while underlying intracranial atherosclerotic stenosis (ICAS; aOR=0.42, 95% CI 0.22 to 0.81, p=0.009) and intracranial angioplasty/stenting (aOR=0.37, 95% CI 0.15 to 0.93, p=0.035) were associated with a low risk of PH. Furthermore, patients with PH were associated with a shift towards to worse functional outcome (mRS score 4 vs 3, adjusted common OR (acOR)=2.27, 95% CI 1.53 to 3.38, p<0.001). CONCLUSIONS: In Chinese patients with AIS caused by anterior circulation LVO, the risk of PH was positively associated with low admission ASPECTS, serum glucose >7 mmol/L, and NLR, but negatively related to underlying ICAS and intracranial angioplasty/stenting. TRIAL REGISTRATION NUMBER: NCT03370939.

13.
Exp Ther Med ; 23(1): 95, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34976137

RESUMO

[This corrects the article DOI: 10.3892/etm.2017.5554.].

14.
Artigo em Inglês | MEDLINE | ID: mdl-35047043

RESUMO

Objective: By integrating meta-analysis and network pharmacology strategy, the clinical efficacy of Zhishe Tongluo capsule in the treatment of cerebral infarction was evaluated, and the intervention mechanism was preliminary explored. Methods: Through meta-analysis, the Chinese and English literature of the randomized controlled trial (RCT) of Zhishe Tongluo capsule in the treatment of cerebral infarction was comprehensively searched. Based on the standard of Na Pai, the quantitative literature was determined and the Review Manager data were statistically analyzed. Results: A total of 10 RCTs literatures were included. These literatures included a total of 1278 subjects, of which 670 were in the treatment group and 608 were in the control group. In terms of indicators of efficiency and adverse reaction rate, the treatment group was better than the control group. There was a statistical difference (P < 0.05); a total of 559 chemical constituents and 2306 potential targets were obtained from the online database. Of these, 201 components, 145 targets, and 185 pathways were closely related to cerebral infarction. Conclusions: The available evidence indicates that the addition of Zhishe Tongluo capsule to the conventional treatment of Western medicine can improve the clinical efficacy of cerebral infarction and has some advantages in regulating blood lipids and hemorheology, but the overall evidence level is low, which still needs to be further supported by large-scale and multicenter RCTs; intervention of brain infarction by Zhishe Tongluo capsule is a comprehensive result of multicomponent and multi-target interactions. On the basis of the combined meta-analysis and network pharmacology in scientific attempts, it also provides a reference for the clinical evaluation of other drugs and mechanism research.

15.
Nanotechnology ; 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35051914

RESUMO

The improvement of electricity production for water evaporation-driven generators (WEGs) remains a challenge. Herein, two types of WEGs were designed to study the resistance matching for improving the electricity production. One type of reduced graphene oxide/carbon nanotube (RGO/CNT) WEG was constructed using RGO with adjustable resistances as working material and CNTs with fixed resistance as electrode material. The other type of graphene oxide (GO)/RGO WEG was constructed using RGO with adjustable resistance as electrode material and GO with fixed resistance was used as working material. The open circuit voltage of RGO/CNT increased from 15 to 56 mV and then decreased to 22 mV with increasing RGO resistance. The short circuit current of RGO/CNT also first increased and then decreased. The performance of GO/RGO was similar with that of RGO/CNT. Typically, the RGO/CNT and GO/RGO WEG showed the highest performance when the working material to electrode material resistance ratio was 2272 and 2365, respectively. It showed that the best resistance ratio of working material to electrode material was in the range of 2000-2500, which helped to improve about 2-5 times of electricity efficiency in the WEG. The present work provides a new direction for optimizing performance of WEGs.

16.
ACS Biomater Sci Eng ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35012306

RESUMO

Bacterial biofilms encased in extracellular polymeric substances to create protected microenvironments are typically challenging to disperse by common antibiotics and cannot be in situ visualized under current modalities. Herein, a pH-responsive branched polymer [poly(MBA-AEPZ)-AEPZ-NA] capable of overcoming antibiotic resistance and real-time visualizing biofilms for fluorescence imaging-guided infection control is reported. The positively charged polymer can effectively penetrate bacterial biofilms, neutralize the anionic character, and then disrupt the structural integrity, thus significantly promoting the transport of antibiotics into biofilms. The polymer shows a weak fluorescence emission intensity under physiological conditions (pH 7.4) but emits intense green-light emission within the localized biofilm microenvironment (pH 5.5) to real-time visualize bacterial biofilms. A therapeutic system made of the polymer and a model antibiotic can significantly reduce the dosages of the drug, thereby minimizing biofilm-induced drug resistance. Notably, a green fluorescent polymer responding to localized pH conditions is demonstrated in living zebrafish. This work confirmed that combinations of the pH-responsive branched polymer and antibiotics could be administered to overcome drug resistance and realize fluorescence imaging-guided treatment of bacterial biofilm infections.

17.
Environ Health Perspect ; 130(1): 17007, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35037767

RESUMO

BACKGROUND: The gut microbiome is important in modulating health in childhood. Metal exposures affect multiple health outcomes, but their ability to modify bacterial communities in children is poorly understood. OBJECTIVES: We assessed the associations of childhood and perinatal blood metal levels with childhood gut microbiome diversity, structure, species, gene family-inferred species, and potential pathway alterations. METHODS: We assessed the gut microbiome using 16S rRNA gene amplicon sequencing and shotgun metagenomic sequencing in stools collected from 6- to 7-year-old children participating in the GESTation and Environment (GESTE) cohort study. We assessed blood metal concentrations [cadmium (Cd), manganese (Mn), mercury (Hg), lead (Pb), selenium (Se)] at two time points, namely, perinatal exposures at delivery (N=70) and childhood exposures at the 6- to 7-y follow-up (N=68). We used multiple covariate-adjusted statistical models to determine microbiome associations with continuous blood metal levels, including linear regression (Shannon and Pielou alpha diversity indexes), permutational multivariate analysis of variance (adonis; beta diversity distance matrices), and multivariable association model (MaAsLin2; phylum, family, species, gene family-inferred species, and pathways). RESULTS: Children's blood Mn and Se significantly associated with microbiome phylum [e.g., Verrucomicrobiota (coef=-0.305, q=0.031; coef=0.262, q=0.084, respectively)] and children's blood Mn significantly associated with family [e.g., Eggerthellaceae (coef=-0.228, q=0.052)]-level differences. Higher relative abundance of potential pathogens (e.g., Flavonifractor plautii), beneficial species (e.g., Bifidobacterium longum, Faecalibacterium prausnitzii), and both potentially pathogenic and beneficial species (e.g., Bacteriodes vulgatus, Eubacterium rectale) inferred from gene families were associated with higher childhood or perinatal blood Cd, Hg, and Pb (q<0.1). We found significant negative associations between childhood blood Pb and acetylene degradation pathway abundance (q<0.1). Finally, neither perinatal nor childhood metal concentrations were associated with children's gut microbial inter- and intrasubject diversity. DISCUSSION: Our findings suggest both long- and short-term associations between metal exposure and the childhood gut microbiome, with stronger associations observed with more recent exposure. Future epidemiologic analyses may elucidate whether the observed changes in the microbiome relate to children's health. https://doi.org/10.1289/EHP9674.

18.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(1): 65-70, 2022 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-35038801

RESUMO

Objective: To design a new type of three-dimensional honeycomb guide for percutaneous cannulated screw placement in femoral neck fracture and evaluate its effectiveness. Methods: The clinical data of 40 patients with femoral neck fracture who met the selection criteria between June 2019 and December 2020 were retrospectively analyzed. According to different intraoperative positioning methods, they were divided into control group (20 cases, free hand positioning screws) and study group (20 cases, new guide assisted positioning screws). There was no significant difference in gender, age, side, cause of injury, Garden classification, and time from injury to operation between the two groups ( P>0.05). The operation time, fluoroscopy times, guide needle puncture times, and fracture healing time of the two groups were recorded. The hip function was evaluated by Harris score at last follow-up. At immediate after operation, the following imaging indexes were used to evaluate the accuracy of screw implantation distribution: screw spacing, screw coverage area, distance from screw to cervical cortex, parallelism between screws, and screw to cervical axial deviation. Results: All operations were successfully completed, and the guide needle did not penetrate the femoral neck cortex. There was no significant difference in operation time and fluoroscopy times between the two groups ( P>0.05); the guide needle puncture times in the study group was significantly less than that in the control group ( t=8.209, P=0.000). Imaging detection at immediate after operation showed that the screw spacing and screw coverage area in the study group were significantly greater than those in the control group ( P<0.05); the distance from screw to cervical cortex, parallelism between screws, and screw to cervical axial deviation were significantly smaller than those in the control group ( P<0.05). All patients were followed up 7-25 months, with an average of 19.3 months. There was no significant difference in follow-up time between the two groups ( t=-0.349, P=0.729). There were 2 cases of fracture nonunion in the control group and 1 case in the study group, and the other fractures completely healed. One case of osteonecrosis of the femoral head occurred in the control group. During the follow-up, there was no complication such as vascular and nerve injury, venous thrombosis, screw penetration, withdrawal, breakage, and refracture, etc. There was no significant difference in fracture healing time and Harris score at last follow-up between the two groups ( P>0.05). Conclusion: The new three-dimensional honeycomb guide has the advantages of simple structure and convenient use. It can reduce the puncture times of the guide needle and effectively improve the accuracy distribution of cannulated screw implantation.


Assuntos
Fraturas do Colo Femoral , Parafusos Ósseos , Feminino , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas , Humanos , Gravidez , Estudos Retrospectivos , Resultado do Tratamento
19.
Clin Cancer Res ; 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35046057

RESUMO

PURPOSE: HER2 mutations (HER2mut) induce endocrine resistance in estrogen receptor positive (ER+) breast cancer. EXPERIMENTAL DESIGN: In this single arm multi-cohort phase II trial, we evaluated the efficacy of neratinib plus fulvestrant in patients with ER+/HER2mut, HER2-non-amplified metastatic breast cancer (MBC) in the fulvestrant-treated (n=24) or fulvestrant-naïve cohort (n=11). Patients with ER-negative/HER2mut MBC received neratinib monotherapy in an exploratory ER- cohort (n=5). RESULTS: The clinical benefit rate (CBR: 95% CI) was 38% (18-62%), 30% (7-65%), and 25% (1-81%) in the fulvestrant-treated, fulvestrant-naïve, and ER- cohort, respectively. Adding trastuzumab at progression in 5 patients resulted in 3 partial responses and 1 stable disease {greater than or equal to}24 weeks. CBR appeared positively associated with lobular histology and negatively associated with HER2 L755 alterations. Acquired HER2mut were detected in 5 of 23 patients at progression. CONCLUSION: Neratinib and fulvestrant is active for ER+/HER2mut MBC. Our data supports further evaluation of dual HER2 blockade for the treatment of HER2mut MBC.

20.
Bioengineered ; 13(2): 2917-2926, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35043753

RESUMO

Transcription factor forkhead box protein 1 (FOXP1) has been shown cardiovascular protection. We aimed to analyze the role of FOXP1 in oxidized low-density lipoprotein (ox-LDL)-induced macrophages and its possible regulatory effect on sestrin1 (SESN1) expression. After stimulation with ox-LDL, FOXP1 expression in RAW264.7 cells was evaluated with RT-qPCR and Western blotting. Then, FOXP1 was overexpressed, followed by detection of inflammatory mediator levels using ELISA kits and RT-qPCR. Lipid accumulation was detected with oil red O staining. Additionally, the JASPAR database was used to predict the potential genes that could be transcriptionally regulated by FOXP1. ChIP and luciferase reporter assays were used to verify this combination. To further clarify the regulatory effects of FOXP1 on SESN1 in damage of macrophages triggered by ox-LDL, SESN1 was silenced to determine the inflammation and lipid accumulation under the condition of FOXP1 overexpression. Results indicated that ox-LDL stimulation led to a significant decrease in FOXP1 expression. FOXP1 overexpression notably reduced the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6, accompanied by a decreased in phosphorylated NF-κB p65 expression. Besides, FOXP1-upregulation inhibited lipid accumulation and reduced CD36 expression level in RAW264.7 cells upon ox-LDL stimulation. Moreover, results of ChIP and luciferase reporter assays suggested that FOXP1 could transcriptionally regulate SESN1 expression. Further experiments supported that SESN1 silencing restored the inhibitory effects of FOXP1 overexpression on the inflammation and lipid accumulation in RAW264.7 cells exposed to ox-LDL. Collectively, FOXP1 transcriptionally activates SESN1 for the alleviation of ox-LDL-induced inflammation and lipid accumulation in macrophages.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...