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1.
World Neurosurg ; 180: e429-e439, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37757943

RESUMO

OBJECTIVE: The aim of this study was to compare the biomechanical performance of 6 pedicle screw internal fixation strategies for the treatment of burst fractures of the thoracolumbar spine using finite element (FE) analysis. METHODS: A finite element model of the T11-L3 thoracolumbar segment was established to simulate L1 vertebral burst fractures, and 6 models were conducted under multidirectional loading conditions: P2-D2, P1-D1, P2-D1,P1-D, P1-BF-D1, and P1-UF-D1. The range of motion (ROM) in the T12-L2 region and the von Mises stresses of pedicle screws and rods under the 6 internal fixation models were mainly analyzed. RESULTS: The maximum ROM and von Mises stress were obtained under flexion motion in all models. The P1-BF-D1 model had the least ROM and screw stress. However, when the injured vertebra was not nailed bilaterally, the P1-UF-D1 model had the smallest ROM; the maximum von Mises stress on the screw and rod was remarkably higher than that recorded in the other models. Moreover, the P2-D1 model had a ROM similar to that of the P1-D2 model, but with lower screw stress. The 2 models outperformed the P1-D1 model in all 6 conditions. The P2-D2 model had a similar ROM with the P2-D1 model; nevertheless, the maximum von Mises stress was not substantially reduced. CONCLUSIONS: The P1-BF-D1 model exhibited better stability and less von Mises stress on the pedicle screws and rods, thereby reducing the risk of screw loosening and fracture. The P2-D1 internal fixation approach is recommended when the fractured vertebrae are not nailed bilaterally.


Assuntos
Parafusos Pediculares , Fraturas da Coluna Vertebral , Fusão Vertebral , Humanos , Análise de Elementos Finitos , Vértebras Lombares/cirurgia , Vértebras Lombares/lesões , Vértebras Torácicas/cirurgia , Vértebras Torácicas/lesões , Fenômenos Biomecânicos , Fraturas da Coluna Vertebral/cirurgia , Amplitude de Movimento Articular
2.
World Neurosurg ; 176: e692-e696, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37295468

RESUMO

OBJECTIVE: The aim of this study was to investigate the changes in spine-pelvis sagittal parameters from the standing position to the prone position and to study the relationship between sagittal parameters and immediately postoperative parameters. METHODS: Thirty-six patients with old traumatic spinal fracture combined with kyphosis were enrolled. The preoperative standing position, prone position, and postoperative sagittal parameters of the spine and pelvis, including the local kyphosis Cobb angle (LKCA), thoracic kyphosis angle (TKA), lumbar lordosis angle (LLA), sacral slope (SS), pelvic tilt (PT), pelvic incidence minus lumbar lordosis angle (PI-LLA), and sagittal vertebral axis (SVA), were measured. The data of kyphotic flexibility and correction rate werecollected and analyzed. The parameters of the preoperative standing position, prone position and postoperative sagittal position were analyzed statistically. Correlation analysis and regression analysis of the preoperative standing and prone sagittal parameters and postoperative parameters were conducted. RESULTS: There were significant differences in the preoperative standing position, prone position, and postoperative LKCA and TK. Correlation analysis showed that preoperative sagittal parameters of the standing position and prone position were all correlated with postoperative homogeneity. Flexibility was not related to the correction rate. Regression analysis showed preoperative standing, prone LKCA, and TK were linear with postoperative standing. CONCLUSIONS: The LKCA and TK of old traumatic kyphosis obviously changed from the standing position to the prone position, which were linear with postoperative LKCA and TK and can be used to predict postoperative sagittal parameters. This change should be taken into account in the surgical strategy.


Assuntos
Fraturas Ósseas , Cifose , Lordose , Humanos , Lordose/diagnóstico por imagem , Lordose/cirurgia , Lordose/complicações , Posição Ortostática , Decúbito Ventral , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Cifose/diagnóstico por imagem , Cifose/etiologia , Cifose/cirurgia , Fraturas Ósseas/complicações , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos Retrospectivos
3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-995199

RESUMO

Objective:To explore any effect of supplementing low-frequency repeated transcranial magnetic stimulation (rTMS) with intermittent resistance training on muscle tone and the recovery of motor function among persons with Parkinson′s disease (PD).Methods:A total of 104 PD patients were randomly divided into an observation group and a control group, each of 52. Both groups were treated with conventional drugs and low-frequency rTMS, while the observation group was additionally provided with intermittent resistance training for 8 weeks. Before and after the intervention, the motor functioning of both groups was evaluated using unified Parkinson′s disease rating scale-III (UPDRS-III) and the Berg Balance Scale (BBS). Limb muscle tension was quantified using the modified Ashworth scale (MAS). The subjects′ psychological states were quantified using the exercise self-efficacy scale (ESE), and the modified Barthel index (MBI) was applied to evaluate their ability in the activities of daily living. A 3D motion processing system collected and analyzed data describing each subject′s gait kinematics.Results:After the intervention, significantly greater average improvement was observed in all of the outcome measures among the observation group compared with the control group.Conclusion:Combining intermittent resistance training with low-frequency rTMS can significantly reduce muscle tone and improve the motor functioning of PD patients. The combination is more effective than low-frequency rTMS alone.

4.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1007931

RESUMO

Using digital technologies in concurrently performing missing tooth implantation and preparation of remaining teeth is a solution to reduce the number of visits and improve efficiency. This paper proposes a digital process for simultaneously implanting and preparing teeth. It integrates implant surgical guide and 3D-printed tooth preparation guide into a single guide and completes guided implant placement and precise tooth preparation. Based on "repair-oriented" virtual implant planning, the implant surgical guide can improve the efficiency and predictability of implant placement, and its linear accuracy is about 1 mm. The tooth preparation guide precisely guides tooth preparation and restoration space visualization, ensuring the quality of the tooth preparation. The two guides have different design accuracy requirements, and thus their combination improves the overall guiding accuracy requirements. The concurrent application of the two guides minimizes the clinical operation time, number of visits, and economic burden of patients.


Assuntos
Humanos , Cirurgia Assistida por Computador , Implantação Dentária Endóssea , Impressão Tridimensional , Tecnologia , Preparo do Dente , Desenho Assistido por Computador , Implantes Dentários , Imageamento Tridimensional , Tomografia Computadorizada de Feixe Cônico
5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981638

RESUMO

OBJECTIVE@#To investigate the changes in spinal-pelvic sagittal parameters from preoperative standing to prone position in old traumatic spinal fractures with kyphosis.@*METHODS@#The clinical data of 36 patients admitted between December 2016 and June 2021 for surgical treatment of old traumatic spinal fractures with kyphosis, including 7 males and 29 females, aged from 50 to 79 years (mean, 63.9 years), were retrospectively analyzed. Lesion segments included 2 cases of T 11, 12 cases of T 12, 2 cases of T 11, 12, 4 cases of T 12 and L 1, 12 cases of L 1, 2 cases of L 2, 1 case of L 2, 3, and 1 case of L 3. The disease duration ranged from 4 to 120 months, with an average of 19.6 months. Surgical procedures included Smith-Petersen osteotomy in 4 cases, Ponte osteotomy in 6 cases, pedicle subtraction osteotomy in 2 cases, and improved fourth level osteotomy in 18 cases; the remaining 6 cases were not osteotomized. The bone mineral density ranged from -3.0 to 0.5 T, with a mean of -1.62 T. The spinal-pelvic sagittal parameters from preoperative standing to prone positions were measured, including local kyphosis Cobb angle (LKCA), thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), and PI and LL mismatch (PI-LL). The kyphotic flexibility=(preoperative standing LKCA-preoperative prone LKCA)/preoperative standing LKCA×100%. Spinal-pelvic sagittal parameters were compared between standing position and prone position before operation, and Pearson correlation was used to judge the correlation between the parameters of standing position and prone position before operation.@*RESULTS@#When the position changed from standing to prone, LKCA and TK decreased significantly ( P<0.05), while SS, LL, PT, and PI-LL had no significant difference ( P>0.05). Pearson correlation analysis showed that LL was significantly correlated with SS and PI-LL in both standing and prone positions ( P<0.05), and the correlation strength between LL and SS in prone position was higher than that in standing position. In the standing position, LKCA was significantly correlated with SS and PT ( P<0.05). However, when the position changed from standing to prone, the correlation between LKCA and SS and PT disappeared, while PT and PI-LL was positive correlation ( P<0.05). The kyphotic flexibility was 25.13%-78.79%, with an average of 33.85%.@*CONCLUSION@#For the patients of old traumatic spinal fractures with kyphosis, the preoperative LKCA and TK decrease significantly from standing position to prone position, and the correlation between spinal and pelvic parameters also changed, which should be taken into account in the formulation of preoperative surgical plan.


Assuntos
Masculino , Feminino , Humanos , Fraturas da Coluna Vertebral/cirurgia , Posição Ortostática , Estudos Retrospectivos , Vértebras Lombares/cirurgia , Cifose/cirurgia , Lordose/cirurgia
6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981637

RESUMO

OBJECTIVE@#To investigate the feasibility of predicting proximal junctional kyphosis (PJK) in adults after spinal deformity surgery based on back-forward Bending CT localization images and related predictive indicators.@*METHODS@#A retrospective analysis was performed for 31 adult patients with spinal deformity who underwent posterior osteotomy and long-segment fusion fixation between March 2017 and March 2020. There were 5 males and 26 females with an average age of 62.5 years (range, 30-77 years). The upper instrumented vertebrae (UIV) located at T 5 in 1 case, T 6 in 1 case, T 9 in 13 cases, T 10 in 12 cases, and T 11 in 4 cases. The lowest instrumented vertebrae (LIV) located at L 1 in 3 cases, L 2 in 3 cases, L 3 in 10 cases, L 4 in 7 cases, L 5 in 5 cases, and S 1 in 3 cases. Based on the full-length lateral X-ray film of the spine in the standing position before and after operation and back-forward Bending CT localization images before operation, the sagittal sequence of the spine was obtained, and the relevant indexes were measured, including thoracic kyphosis (TK), lumbar lordosis (LL), local kyphosis Cobb angle (LKCA) [the difference between the different positions before operation (recovery value) was calculated], kyphosis flexibility, hyperextension sagittal vertical axis (hSVA), T 2-L 5 hyperextension C 7-vertebral sagittal offset (hC 7-VSO), and pre- and post-operative proximal junctional angle (PJA). At last follow-up, the patients were divided into PJK and non-PJK groups based on PJA to determine whether they had PJK. The gender, age, body mass index (BMI), number of fusion segments, number of cases with coronal plane deformity, bone mineral density (T value), UIV position, LIV position, operation time, intraoperative blood loss, osteotomy grading, and related imaging indicators were compared between the two groups. The hC 7-VSO of the vertebral body with significant differences between groups was taken, and the receiver operating characteristic curve (ROC) was used to evaluate its accuracy in predicting the occurrence of PJK.@*RESULTS@#All 31 patients were followed up 13-52 months, with an average of 30.0 months. The patient's PJA was 1.4°-29.0° at last follow-up, with an average of 10.4°; PJK occurred in 8 cases (25.8%). There was no significant difference in gender, age, BMI, number of fusion segments, number of cases with coronal plane deformity, bone mineral density (T value), UIV position, LIV position, operation time, intraoperative blood loss, and osteotomy grading between the two groups ( P>0.05). Imaging measurements showed that the LL recovery value and T 8-L 3 vertebral hC 7-VSO in the PJK group were significantly higher than those in the non-PJK group ( P>0.05). There was no significant difference in hyperextension TK, hyperextension LL, hyperextension LKCA, TK recovery value, LL recovery value, kyphosis flexibility, hSVA, and T 2-T 7, L 4, L 5 vertebral hC 7-VSO ( P>0.05). T 8-L 3 vertebral hC 7-VSO was analyzed for ROC curve, and combined with the area under curve and the comprehensive evaluation of sensitivity and specificity, the best predictive index was hC 7-L 2, the cut-off value was 2.54 cm, the sensitivity was 100%, and the specificity was 60.9%.@*CONCLUSION@#Preoperative back-forward Bending CT localization image can be used to predict the occurrence of PJK after posterior osteotomy and long-segment fusion fixation in adult spinal deformity. If the patient's T 8-L 2 vertebral hC 7-VSO is too large, it indicates a higher risk of postoperative PJK. The best predictive index is hC 7-L 2, and the cut-off value is 2.54 cm.


Assuntos
Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Perda Sanguínea Cirúrgica , Vértebras Torácicas/cirurgia , Cifose/cirurgia , Lordose/cirurgia , Fusão Vertebral/métodos , Tomografia Computadorizada por Raios X , Complicações Pós-Operatórias/diagnóstico por imagem , Vértebras Lombares/cirurgia
7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981615

RESUMO

OBJECTIVE@#To introduce a scout view scanning technique of back-forward bending CT (BFB-CT) in simulated surgical position for evaluating the remaining real angle and flexibility of thoracolumbar kyphosis secondary to old osteoporotic vertebral compression fracture.@*METHODS@#A total of 28 patients with thoracolumbar kyphosis secondary to old osteoporotic vertebral compression fracture who met the selection criteria between June 2018 and December 2021 were included in the study. There were 6 males and 22 females with an average age of 69.5 years (range, 56-92 years). The injured vertebra were located at T 10-L 2, including 11 cases of single thoracic fracture, 11 cases of single lumbar fracture, and 6 cases of multiple thoracolumbar fractures. The disease duration ranged from 3 weeks to 36 months, with a median of 5 months. All patients received examinations of BFB-CT and standing lateral full-spine X-ray (SLFSX). The thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), local kyphosis of injured vertebra (LKIV), lumbar lordosis (LL), and the sagittal vertical axis (SVA) were measured. Referring to the calculation method of scoliosis flexibility, the kyphosis flexibility of thoracic, thoracolumbar, and injured vertebra were calculated respectively. The sagittal parameters measured by the two methods were compared, and the correlation of the parameters measured by the two methods was analyzed by Pearson correlation.@*RESULTS@#Except LL ( P>0.05), TK, TLK, LKIV, and SVA measured by BFB-CT were significantly lower than those measured by SLFSX ( P<0.05). The flexibilities of thoracic, thoracolumbar, and injured vertebra were 34.1%±18.8%, 36.2%±13.8%, and 39.3%±18.6%, respectively. Correlation analysis showed that the sagittal parameters measured by the two methods were positively correlated ( P<0.001), and the correlation coefficients of TK, TLK, LKIV, and SVA were 0.900, 0.730, 0.700, and 0.680, respectively.@*CONCLUSION@#Thoracolumbar kyphosis secondary to old osteoporotic vertebral compression fracture shows an excellent flexibility and BFB-CT in simulated surgical position can obtain the remaining real angle which need to be corrected surgically.


Assuntos
Masculino , Feminino , Humanos , Idoso , Fraturas por Compressão/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vértebras Torácicas/cirurgia , Cifose/cirurgia , Fraturas por Osteoporose/cirurgia , Lordose , Tomografia Computadorizada por Raios X , Estudos Retrospectivos
8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981614

RESUMO

OBJECTIVE@#To analyze the correlation between bone cement cortical leakage and injury degree of osteoporotic vertebral compression fracture (OVCF) after percutaneous kyphoplasty (PKP), and to provide guidance for reducing clinical complications.@*METHODS@#A clinical data of 125 patients with OVCF who received PKP between November 2019 and December 2021 and met the selection criteria was selected and analyzed. There were 20 males and 105 females. The median age was 72 years (range, 55-96 years). There were 108 single-segment fractures, 16 two-segment fractures, and 1 three-segment fracture. The disease duration ranged from 1 to 20 days (mean, 7.2 days). The amount of bone cement injected during operation was 2.5-8.0 mL, with an average of 6.04 mL. Based on the preoperative CT images, the standard S/H ratio of the injured vertebra was measured (S: the standard maximum rectangular area of the cross-section of the injured vertebral body, H: the standard minimum height of the sagittal position of the injured vertebral body). Based on postoperative X-ray films and CT images, the occurrence of bone cement leakage after operation and the cortical rupture at the cortical leakage site before operation were recorded. The correlation between the standard S/H ratio of the injured vertebra and the number of cortical leakage was analyzed.@*RESULTS@#Vascular leakage occurred in 67 patients at 123 sites of injured vertebrae, and cortical leakage in 97 patients at 299 sites. Preoperative CT image analysis showed that there were 287 sites (95.99%, 287/299) of cortical leakage had cortical rupture before operation. Thirteen patients were excluded because of vertebral compression of adjacent vertebrae. The standard S/H ratio of 112 injured vertebrae was 1.12-3.17 (mean, 1.67), of which 87 cases (268 sites) had cortical leakage. The Spearman correlation analysis showed a positive correlation between the number of cortical leakage of injured vertebra and the standard S/H ratio of injured vertebra ( r=0.493, P<0.001).@*CONCLUSION@#The incidence of cortical leakage of bone cement after PKP in OVCF patients is high, and cortical rupture is the basis of cortical leakage. The more severe the vertebral injury, the greater the probability of cortical leakage.


Assuntos
Masculino , Feminino , Humanos , Idoso , Cifoplastia/métodos , Cimentos Ósseos , Fraturas por Compressão/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Estudos Retrospectivos , Fraturas por Osteoporose/etiologia , Resultado do Tratamento , Vertebroplastia/métodos
9.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-981129

RESUMO

OBJECTIVES@#The objectives of this study were to assess the quality of prosthetic prescriptions of removable partial dentures (RPDs) and to analyze the current situation of the communication and information delivery between clinicians and technicians.@*METHODS@#All RPD prosthetic prescriptions received by a major dental laboratory in 4 weeks were involved in a quality audit, and the prescriptions were divided into three groups in accordance with the grades of clients. The filling of prosthetic prescriptions was recorded. The items in the prescriptions for audit included the general information of the patient, the general information of the clinician, the design diagram information, other detailed information, and the return date. The prescriptions were categorized into four levels on the basis of their quality by two quality inspectors who have been working for more than 10 years.@*RESULTS@#A total of 916 prescriptions were collected and assessed. The names in the general information of the patient and the clinician were filled out best, both at the rate of 97.6% (n=894). The return date was filled out worst, only at the rate of 6.4% (n=59). Of those prescriptions, 86.8% (n=795) exhibited inadequate design diagram information. The results of the quality assessment demonstrated that 74.2% of prescriptions were assessed as noncompliant ones and failed to meet the acceptable clinical quality standard.@*CONCLUSIONS@#At present, the overall quality of RPD prosthetic prescriptions is poor. The responsibilities of clinicians and technicians are unclear, and the communication between them is not ideal.


Assuntos
Humanos , Planejamento de Dentadura , Prótese Parcial Removível , Prescrições
10.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-981104

RESUMO

When selecting implant guidance methods or judging whether the patient can be implanted, many doctors ignore or only use visual inspection to estimate a patient's mouth opening. This phenomenon often leads to failure to complete the implantation due to insufficient mouth opening or the deflection of the implant due to limited angle, resulting in the high incidence of corresponding complications. The main reason is that doctors lack accurate analysis and control of the overall geometric conditions of the intraoral surgical area, and three-dimensional position blocking of surgical instruments occurs during the operation. In the past, mouth opening was defined as the distance between the incisor edges of the upper and lower central incisors when the patient opens his mouth widely, and the implant area could be in any missing tooth position. When it is in the posterior tooth area, the specific measurement scheme of the mouth opening could not be simply equivalent to the previous measurement method in the anterior tooth area. However, how to measure quickly and conveniently the mouth opening of any surgical area to determine whether it could be implanted and meet the needs of the selected guidance method remains unclear. This paper introduces new concepts, establishes new classification and corresponding accurate measurement scheme of implant area, and establishes a decision tree of implant methods guided by the actually measured value. Results provide a quantitative basis for rational formulation and implementation of implant treatment.


Assuntos
Humanos , Boca , Implantação Dentária Endóssea/métodos , Incisivo , Tomada de Decisão Clínica , Implantes Dentários
11.
Medicine (Baltimore) ; 101(47): e32059, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36451478

RESUMO

To analyze the pharmacological mechanism of Epimedium in regulating heart failure (HF) based on the network pharmacology method, and to provide a reference for the clinical application of Epimedium in treating HF. Obtaining the main active ingredients and their targets of Epimedium through TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) database. Access to major HF targets through Genecards, OMIM, PharmGKB, Therapeutic Target Database, Drug Bank database. Protein interaction analysis using String platform and construction of PPI network. Subsequently, Cytoscape software was used to construct the "Epimedium active ingredient-heart failure target" network. Finally, the molecular docking is verified through the Systems Dock Web Site. The core active ingredients of Epimedium to regulate HF are quercetin, luteolin, kaempferol, etc. The core targets are JUN, MYC, TP53, HIF1A, ESR1, RELA, MAPK1, etc. Molecular docking validation showed better binding activity of the major targets of HF to the core components of Epimedium. The biological pathways that Epimedium regulates HF mainly act on lipid and atherosclerotic pathways, PI3K-Akt signaling pathway, and chemoattractant-receptor activation. And its molecular functions are mainly DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, and neurotransmitter receptor activity. This study reveals the multi-component, multi-target and multi-pathway mechanism of action of Epimedium in regulating mental failure, and provides a basis for the clinical development and utilization of Epimedium to intervene in HF.


Assuntos
Epimedium , Insuficiência Cardíaca , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Tecnologia , Insuficiência Cardíaca/tratamento farmacológico , Fatores de Transcrição , DNA
12.
Medicine (Baltimore) ; 101(41): e31097, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36254001

RESUMO

Heart failure is a global health problem and the number of sufferers is increasing as the population grows and ages. Existing diagnostic techniques for heart failure have various limitations in the clinical setting and there is a need to develop a new diagnostic model to complement the existing diagnostic methods. In recent years, with the development and improvement of gene sequencing technology, more genes associated with heart failure have been identified. We screened for differentially expressed genes in heart failure using available gene expression data from the Gene Expression Omnibus database and identified 6 important genes by a random forest classifier (ASPN, MXRA5, LUM, GLUL, CNN1, and SERPINA3). And we have successfully constructed a new heart failure diagnostic model using an artificial neural network and validated its diagnostic efficacy in a public dataset. We calculated heart failure-related differentially expressed genes and obtained 24 candidate genes by random forest classification, and selected the top 6 genes as important genes for subsequent analysis. The prediction weights of the genes of interest were determined by the neural network model and the model scores were evaluated in 2 independent sample datasets (GSE16499 and GSE57338 datasets). Since the weights of RNA-seq predictions for constructing neural network models were theoretically more suitable for disease classification of RNA-seq data, the GSE57338 dataset had the best performance in the validation results. The diagnostic model derived from our study can be of clinical value in determining the likelihood of HF occurring through cardiac biopsy. In the meantime, we need to further investigate the accuracy of the diagnostic model based on the results of our study.


Assuntos
Insuficiência Cardíaca , Redes Neurais de Computação , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/genética , Humanos
13.
Acta Pharmaceutica Sinica B ; (6): 532-557, 2022.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-929313

RESUMO

Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

14.
Nat Commun ; 12(1): 4722, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354059

RESUMO

Mutations in the LaminA gene are a common cause of monogenic dilated cardiomyopathy. Here we show that mice with a cardiomyocyte-specific Lmna deletion develop cardiac failure and die within 3-4 weeks after inducing the mutation. When the same Lmna mutations are induced in mice genetically deficient in the LINC complex protein SUN1, life is extended to more than one year. Disruption of SUN1's function is also accomplished by transducing and expressing a dominant-negative SUN1 miniprotein in Lmna deficient cardiomyocytes, using the cardiotrophic Adeno Associated Viral Vector 9. The SUN1 miniprotein disrupts binding between the endogenous LINC complex SUN and KASH domains, displacing the cardiomyocyte KASH complexes from the nuclear periphery, resulting in at least a fivefold extension in lifespan. Cardiomyocyte-specific expression of the SUN1 miniprotein prevents cardiomyopathy progression, potentially avoiding the necessity of developing a specific therapeutic tailored to treating each different LMNA cardiomyopathy-inducing mutation of which there are more than 450.


Assuntos
Cardiomiopatia Dilatada/genética , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Animais , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/fisiopatologia , Dependovirus/genética , Feminino , Humanos , Lamina Tipo A/deficiência , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/deficiência , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Transdução Genética
15.
Rev. habanera cienc. méd ; 20(4): e3867, 2021.
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1289623

RESUMO

Introducción: Desde hace más de 15 años, las vacunas antineumocócicas conjugadas (PCVs) están disponibles en muchas partes del mundo, y son efectivas en la prevención de las enfermedades neumocócicas en niños. La OMS recomienda la inclusión de las PCVs en los programas de inmunización infantil en todo el mundo. Objetivo: Valorar el abordaje ético y el impacto socioeconómico de las vacunas antineumocócicas conjugadas para la decisión de uso en diferentes contextos. Material y Métodos: Se realizó una búsqueda bibliográfica en las bases de datos PubMed y SciELO, considerando informes de la web de la OMS. Desarrollo: Está globalmente considerado que para la reglamentación, el desarrollo y el uso de las PCVs,se deben tener en cuenta aspectos regulatorios, resultados de investigaciones y el consentimiento informado (CI) de los sujetos. En el contexto de países como China,la PCV13 de la empresa Pfizer es de la Clase II debido a su alto precio de importación, en otros contextos como Cuba no se ha introducido la vacunación contra neumococo por limitaciones financieras. Los equipos de investigación trabajan en el desarrollo de las PCVs para reducir el coste de la importación de estas vacunas, haciendo realidad la inclusión de las PCVs en el programa nacional de inmunización. A pesar de complejidad cada vez mayor de la investigación vacunológica, los investigadores seguirán obligados a adherirse a los principios éticos. Conclusiones: Es necesario una vacuna antineumocócica conjugada más económica para tener un impacto socio-económico más alto. Los profesionales sanitarios tienen la obligación de ser éticos y rigurosos en las investigaciones vacunológicas. Además, estas investigaciones requieren de la revisión por parte de un consejo de revisión ética a escala nacional y su seguimiento debe ser sistemático. Cabe señalar que los estudios en población infantil deben ser fuertemente regulados y controlados(AU)


Introduction: Pneumococcal conjugate vaccines (PCVs) have been available in many parts of the world for more than 15 years and are effective in preventing pneumococcal diseases in children. The WHO recommends the inclusion of PCVs in childhood immunization programmes worldwide. Objective: To value the approach to ethics and the socioeconomic impact of the conjugate pneumococcal vaccines. Material and Methods: A bibliographic review was carried out in databases such as PubMed and SciELO, considering reports from the WHO website. Development: It is globally considered that regulatory aspects, research results and informed consent (IC) of the subjects should be taken into account for the regulation, development and use of PCVs. In the context of countries such as China,the PCV13 of the Pfizer company is Class II due to its high import price. In other contexts, such as Cuba, pneumococcal vaccination has not been introduced due to financial limitations. Research teams are working on the development of PCVs to reduce the cost of importing these vaccines, making the inclusion of PCVs in the national immunization program a reality. Despite the increasing complexity of vaccinology research, researchers will continue to be obliged to adhere to ethical principles. Conclusions: A cheaper pneumococcal conjugate vaccine would be needed to have a higher socioeconomic impact. Healthcare professionals have the obligation to be ethical and rigorous in vaccinology research. In addition, such research requires review by a national ethical review board and should be systematically monitored. It should be noted that studies in the pediatric population should be strongly regulated and controlled(AU)


Assuntos
Humanos , Infecções Pneumocócicas/prevenção & controle , Controle Social Formal , Programas de Imunização , Atenção à Saúde
16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-908454

RESUMO

Gallbladder-duodenal fistula is a rare disease in clinical practice, and difficult to diagnosis. One patient with high suspicion of gallbladder-duodenal fistula in preoperative examination was performed with percutaneous transhepatic gallbladder drainage due to could not tolerate surgical operation, and gallbladder-duodenal fistula was diagnosed with the gastric and intestinal fluids extracted from the drainage tube. In the later of fistula repair and the patient′s nutritional support management, the jejunal nutrition tube is inserted through the bile duct, and then the nutrition support was performed through this jejunal nutrition tube. This patients was recovered well.

17.
Can Respir J ; 2020: 9705604, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32831980

RESUMO

Background: Asthma and diabetes are both diseases that affect a wide range of people worldwide. As a common treatment for diabetes, metformin has also been reported to be effective in improving asthma outcomes. We conducted a combined analysis to examine the efficacy of metformin in reducing asthma exacerbation in patients with concurrent asthma and diabetes. Methods: We searched the PubMed, Embase, and CENTRAL databases for articles published prior to April 2020 to find observational studies of individuals with concurrent asthma and diabetes that compared the risk of asthma exacerbation between metformin users and nonusers. Two researchers separately screened the studies, extracted data, and evaluated the risk of bias. The primary outcome was the adjusted risk of asthma exacerbation. The secondary outcomes were the adjusted risk of asthma-related hospitalization and emergency room visits. Review Manager was used for data analysis and plotting. I 2 and χ 2 tests were used to estimate heterogeneity. A random effects or fixed effects model was used depending on the heterogeneity. Odds ratios were calculated for dichotomous variables. Results: We included two studies with a total of 25252 patients. The pooled effect size showed that metformin was inversely associated with a risk of asthma exacerbation (OR = 0.65, 95% CI 0.28-1.48; χ 2 = 5.42, P=0.02; I 2 = 82%), asthma-related emergency department visits (OR = 0.81, 95% CI 0.74-0.89; χ 2 = 0.36, P=0.55; I 2 = 0%), and hospitalizations (OR = 0.43, 95% CI 0.14-1.29; χ 2 = 4.01, P=0.05; I 2 = 75%). Conclusion: This meta-analysis suggested that metformin decreased the risk of asthma-related emergency room visits for patients with concurrent asthma and diabetes. Metformin reduced the risk of asthma-related hospitalization and exacerbation but was not statistically significant. More randomized trials involving larger samples should be considered, and the mechanisms of these effects need to be fully elucidated.


Assuntos
Asma/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/uso terapêutico , Asma/complicações , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Humanos , Estudos Observacionais como Assunto , Fatores de Risco
18.
Rev Esp Salud Publica ; 942020 Jul 02.
Artigo em Espanhol | MEDLINE | ID: mdl-32613951

RESUMO

Today, the novel coronavirus has spread widely throughout the world and poses new challenges to ensure the health and safety of health personnel. Because health personnel are at the frontlines in the fight against the novel coronavirus, which is one of the groups most affected and vulnerable during the pandemic, it is necessary to remind that the preventive measures adopted by health personnel are essential. Especially in emergency situations, essential measures must be taken to prevent occupational exposure during the novel coronavirus pandemic. Health professionals are working with great intensity and enormous social responsibility. In addition to the applause, they deserve more attention.


Al día de hoy, el nuevo coronavirus SARS-CoV-2 se ha extendido ampliamente por el mundo y plantea nuevos desafíos para garantizar la salud y seguridad del personal sanitario. Debido a que dicho personal está en primera línea de la lucha contra el nuevo coronavirus, siendo uno de los grupos más afectados y vulnerables durante la pandemia, es necesario tener en cuenta que las medidas preventivas adoptadas por ellos son fundamentales. Especialmente en situaciones de emergencia, hay que tomar las medidas imprescindibles para la prevención de la exposición ocupacional durante esta nueva pandemia. Los profesionales sanitarios están trabajando con una gran intensidad y una enorme responsabilidad social pero, además de los aplausos, merecen más atención.


Assuntos
Infecções por Coronavirus/prevenção & controle , Pessoal de Saúde , Hospitais , Exposição Ocupacional/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus , COVID-19 , Humanos , SARS-CoV-2 , Espanha
19.
China Occupational Medicine ; (6): 390-395, 2020.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-881910

RESUMO

OBJECTIVE: To investigate the effects of combined exposure to di(2-ethylhexyl) phthalate(DEHP) and bisphenol A(BPA) on glucose metabolism in female rats during gestational and lactation periods, and its possible mechanism. METHODS: Twenty-four specific pathogen free pregnant SD rats were randomly divided into control group, DEHP group, BPA group, and combined exposure group, with 6 rats in each group. From the 5 th day of gestation to the 21 st day after birth of the offspring, the rats in the DEHP group were treated with DEHP 600 mg/kg body weight(bw); rats in BPA group were treated with 80 mg/kg bw BPA, and rats in combined exposure group were treated with 600 mg/kg bw DEHP and 80 mg/kg bw BPA by intragastric perfusion, while the rats in the control group were given the same amount of corn oil, once per day. After exposure, maternal rats were sacrificed immediately. The levels of glucose metabolism related indicators in liver tissues and serum were examined, and the mRNA and protein expression of phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(AKT) signaling pathway related factors in liver tissues were detected by real-time fluorescence quantitative polymerase chain reaction and Western blot. RESULTS: Except for the activity of phosphoenolpyruvate carboxykinase(PEPCK) in BPA group, the levels of liver glycogen and serum high density lipoprotein cholesterol(HDL-C) in rats of the 3 exposure groups decreased(P<0.05), while the activity of serum PEPCK and the level of low density lipoprotein cholesterol(LDL-C) increased(P<0.05) compared with rats in the control group. The levels of liver glycogen and serum HDL-C in the combined exposure group were lower than that in the BPA group(P<0.05), while the level of serum LDL-C were lower than that in DEHP group and BPA group(P<0.05). The levels of serum glycosylated serum protein, total cholesterol and triglyceride in the 4 groups were not statistically different when compared with each other(P>0.05). Except for the PI3 K protein in DEHP group, the mRNA and protein expression of PI3 K, AKT, and glucose transporter 4 in liver tissues of rats in the 3 exposure groups decreased(P<0.05), and the mRNA expression of forkhead box protein 1(Foxo1) decreased(P<0.05), but the protein expression of FOXO1 increased(P<0.05) compared with the control group. CONCLUSION: Exposure to DEHP or BPA during pregnancy and lactation can cause glucose metabolism disorders in rats. The combined exposure of DEHP and BPA has certain synergistic effect. This process may be achieved through the PI3 K/AKT signaling pathway.

20.
China Occupational Medicine ; (6): 428-433, 2019.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-881813

RESUMO

OBJECTIVE: To investigate the mechanism of calcium ion(Ca~(2+))/calcineurin(CaN) signaling pathway in bisphenol A(BPA)-induced interleukin-6(IL-6) secretion in macrophages. METHODS: Raw 264.7 cells in logarithmic growth phase were divided into control group, activator group, BPA low-, medium-and high-dose groups and inhibitor group. The cells in control group were treated with 0.10% dimethyl sulfoxide. The activator group was treated with lipopolysaccharide at mass concentration of 2 mg/L. The 3 BPA groups were treated with BPA at final concentrations of 1, 10, or 100 μmol/L. Two sets of verapamil or tacrolimus(FK506) groups were given verapamil at the final concentration of 10 or 30 μmol/L; or final concentration of FK506 at 250 or 500 nmol/L. Then the cells were treated with final concentration of 100 μmol/L BPA. The cells were collected at 4, 12, and 24 hours. The mRNA expression of IL-6 and CaN at 4 and 12 hours were detected by real-time fluorescence quantitative polymerase chain reaction. The relative expression of IL-6 and CaN protein was detected at 24 hours by enzyme-linked immunosorbent assay, and the intracellular Ca~(2+) level was detected at 4 hours using a single-tube multi-function detector. RESULTS: At 12 hours, the mRNA expression of IL-6 in the 100 μmol/L BPA group was higher than that in control group, activator group and the 1 and 10 μmol/L BPA groups(P<0.05), and higher than that in the 10 and 30 μmol/L verapamil groups, and in the 250 and 500 nmol/L FK506 groups(P<0.05). The mRNA expression of CaN in the 100 μmol/L BPA group was higher than that in control group, activator group and 1 and 10 μmol/L BPA groups(P<0.05), and higher than in 10 and 30 μmol/L verapamil groups(P<0.05). The relative expression of IL-6 protein in the 100 μmol/L BPA group was higher than that in control group, activator group and 1 and 10 μmol/L BPA groups(P<0.05). The relative expression of CaN protein in 100 μmol/L BPA group and 10 and 30 μmol/L verapamil groups were higher than that in control group and activator group(P<0.05). The relative expression of CaN protein in the 10 and 30 μmol/L verapamil groups were lower than that in the 100 μmol/L BPA group(P<0.05). The intracellular Ca~(2+) level in the 100 μmol/L BPA group was higher than that in control group and activator group(P<0.05). The intracellular Ca~(2+) level in the 10 μmol/L verapamil group was lower than that in the 100 μmol/L BPA group(P<0.05). CONCLUSION: BPA might promote the secretion of IL-6 through Ca~(2+)/CaN signaling pathway in macrophages.

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