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1.
Nature ; 622(7984): 850-862, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37794185

RESUMO

Immune checkpoint blockade is effective for some patients with cancer, but most are refractory to current immunotherapies and new approaches are needed to overcome resistance1,2. The protein tyrosine phosphatases PTPN2 and PTPN1 are central regulators of inflammation, and their genetic deletion in either tumour cells or immune cells promotes anti-tumour immunity3-6. However, phosphatases are challenging drug targets; in particular, the active site has been considered undruggable. Here we present the discovery and characterization of ABBV-CLS-484 (AC484), a first-in-class, orally bioavailable, potent PTPN2 and PTPN1 active-site inhibitor. AC484 treatment in vitro amplifies the response to interferon and promotes the activation and function of several immune cell subsets. In mouse models of cancer resistant to PD-1 blockade, AC484 monotherapy generates potent anti-tumour immunity. We show that AC484 inflames the tumour microenvironment and promotes natural killer cell and CD8+ T cell function by enhancing JAK-STAT signalling and reducing T cell dysfunction. Inhibitors of PTPN2 and PTPN1 offer a promising new strategy for cancer immunotherapy and are currently being evaluated in patients with advanced solid tumours (ClinicalTrials.gov identifier NCT04777994 ). More broadly, our study shows that small-molecule inhibitors of key intracellular immune regulators can achieve efficacy comparable to or exceeding that of antibody-based immune checkpoint blockade in preclinical models. Finally, to our knowledge, AC484 represents the first active-site phosphatase inhibitor to enter clinical evaluation for cancer immunotherapy and may pave the way for additional therapeutics that target this important class of enzymes.


Assuntos
Imunoterapia , Neoplasias , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Proteína Tirosina Fosfatase não Receptora Tipo 2 , Animais , Humanos , Camundongos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos , Inibidores de Checkpoint Imunológico , Imunoterapia/métodos , Interferons/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Neoplasias/imunologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 2/antagonistas & inibidores , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
2.
Eur Radiol ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374482

RESUMO

OBJECTIVES: To evaluate the additional advantages of integrating contrast-enhanced ultrasound (CEUS) into the Ovarian-Adnexal Reporting and Data System (O-RADS) ultrasound (US) for the characterization of adnexal lesions with solid components. MATERIALS AND METHODS: This prospective multicenter study recruited women suspected of having adnexal lesions with solid components between September 2021 and December 2022. All patients scheduled for surgery underwent preoperative CEUS and US examinations. The lesions were categorized according to the O-RADS US system, and quantitative CEUS indexes were recorded. Pathological results served as the reference standard. Univariable and multivariable analyses were performed to identify risk factors for malignancy in adnexal lesions with solid components. Receiver operating characteristic (ROC) curve analysis was employed to assess diagnostic performance. RESULTS: A total of 180 lesions in 175 women were included in the study. Among these masses, 80 were malignant and 100 were benign. Multivariable analysis revealed that serum CA-125, the presence of acoustic shadowing, and peak intensity (PI) ratio (PImass/PIuterus) of solid components on CEUS were independently associated with adnexal malignancy. The modified CEUS risk stratification model demonstrated superior diagnostic value in assessing adnexal lesions with solid components compared to O-RADS US (AUC: 0.91 vs 0.78, p < 0.001) and exhibited comparable performance to the Assessment of Different NEoplasias in the adnexa (ADNEX) model (AUC 0.91 vs 0.86, p = 0.07). CONCLUSION: Our findings underscore the potential value of CEUS as an adjunctive tool for enhancing the precision of diagnostic evaluations of O-RADS US. CLINICAL RELEVANCE STATEMENT: The promising performance of the modified CEUS risk stratification model suggests its potential to mitigate unnecessary surgeries in the characterization of adnexal lesions with solid components. KEY POINTS: • The additional value of CEUS to O-RADS US in distinguishing between benign and malignant adnexal lesions with solid components requires further evaluation. • The modified CEUS risk stratification model displayed superior diagnostic value and specificity in characterizing adnexal lesions with solid components when compared to O-RADS US. • The inclusion of CEUS demonstrated potential in reducing the need for unnecessary surgeries in the characterization of adnexal lesions with solid components.

3.
J Orthop Sci ; 29(2): 537-541, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37003851

RESUMO

INTRODUCTION: After surgical fixation of distal radius fractures, many patients are keen to return to driving. There are however limited guidelines assisting surgeons. The aims of this study were to determine when patients could return to driving safely after distal radius fracture fixation and determine the clinical parameters (range of motion and grip strength) that patients needed to achieve before return to safe driving could be advised. MATERIALS AND METHODS: A prospective grant-funded clinical study was conducted. Patients above the age of 21 years who underwent surgical fixation with a volar plate, possessed a class 3 standard motorcar license, and were regular drivers were recruited in a single institution from 2017 to 2019. A hand surgeon and an occupational therapist who sees routine hand therapy cases, assessed the patients at regular intervals from 2 to 12-weeks post-surgery. Clinical parameters of pain, wrist range of motion and grip strength were measured. Patients underwent off and on-road driving assessments. RESULTS: A total of 26 patients were recruited, with 21 successfully completing the driving assessment. Median time post-surgery to passing the driving test was 6 and 8-weeks for off and on-road assessments respectively. Pain score was observed to decrease over time, with a significant decrease from week 2 to week 4. Range of motion improved over time, with maximal improvement between 2 to 4-weeks post-surgery. When compared with the unaffected wrist, the difference in pronation, supination and radial deviation in the affected hand was consistently no longer statistically significant 4 to 6-weeks post-surgery. CONCLUSION: Patients with isolated surgically treated distal radius fractures can be recommended for a driving assessment as early as 4-6 weeks post-surgery if pain control is adequate, and clinical parameters for pronation and supination are met.


Assuntos
Fraturas do Rádio , Fraturas do Punho , Humanos , Adulto Jovem , Adulto , Estudos Prospectivos , Fraturas do Rádio/cirurgia , Fraturas do Rádio/etiologia , Fixação Interna de Fraturas/efeitos adversos , Força da Mão , Placas Ósseas , Amplitude de Movimento Articular , Dor/etiologia , Resultado do Tratamento
4.
J Sports Sci Med ; 22(4): 748-759, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38045742

RESUMO

This study sought to provide a comprehensive assessment of the incidence of sports injuries among athletes participating in the Olympic Winter Games and to investigate contributing factors. We gathered injury data from athletes participating in the recent four Olympic Winter Games, incorporating details on the sports event, sex, injury location, and type. Through a meta-analysis, we calculated the injury incidence rates for each sport and examined the influence of sex and the type of sport on these incidence rates. Out of 11,197 registered athletes, we documented 1,304 sports injuries. The sports events with the highest injury rates were freestyle skiing, snowboarding, alpine skiing, bobsleigh, and ice hockey, with the most frequent injury locations being the knees, thoracic/lumbar/back regions, and the wrist/hand/fingers. Contusions, hematomas, and bruises were the most prevalent injuries, followed by strains (including muscle rupture, tearing, or tendon rupture) and sprains (covering dislocations, subluxations, and ligament ruptures). In the Olympic Winter Games, events such as freestyle skiing, snowboarding, alpine skiing, bobsleigh, and ice hockey pose a particularly high risk. Predominant injury sites include the knee, spine/back, and wrist and hand, with injuries ranging from contusions and hematomas to strains and sprains. For effective injury prevention, it is crucial to emphasize proper medical resource allocation, specialized training for medical personnel, and meticulous venue maintenance.


Assuntos
Traumatismos em Atletas , Contusões , Esportes na Neve , Entorses e Distensões , Humanos , Traumatismos em Atletas/epidemiologia , Traumatismos em Atletas/etiologia , Atletas , Entorses e Distensões/epidemiologia , Contusões/complicações , Hematoma/complicações
5.
BMC Cancer ; 22(1): 240, 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35246056

RESUMO

BACKGROUND: Bladder Cancer (BCa) is a severe genitourinary tract disease with an uncertain pathology. Increasing evidence indicates that the tumor microenvironment plays a decisive role with respect to cancer progression, and that this is driven by tumor cell interactions with stromal components. Tenascin-C (TN-C) is an important extracellular matrix (ECM) component, which has been reported to be involved in other types of cancer, such as breast cancer. The expression of TN-C in BCa tissue has been reported to be positively associated with the BCa pathological grade, yet the presence of urine TN-C is considered as an independent risk factor for BCa. However, the role of TN-C in BCa progression is still unknow. Thus, the object of the present investigation is to determine the role of TN-C in BCa progression and the involved mechanism. METHODS: In this study, expression of TN-C in BCa tissue of Chinese local people was determined by IHC. Patients corresponding to tumor specimens were flowed up by telephone call to get their prognostic data and analyzed by using SPSS 19.0 statistic package. In vitro mechanistic investigation was demonstrated by QT-qPCR, Western Blot, Plasmid transfection to establishment of high/low TN-C-expression stable cell line, Boyden Chamber Assay, BrdU incorporation, Wound Healing, laser scanning confocal microscopy (LSCM) and ELISA. RESULTS: TN-C expression in BCa tissue increases with tumor grade and is an independent risk factor for BCa patient. The in vitro investigation suggested that TN-C enhances BCa cell migration, invasion, proliferation and contributes to the elevated expression of EMT-related markers by activating NF-κB signaling, the mechanism of which involving in syndecan-4. CONCLUSIONS: Expression of TN-C in BCa tissues of Chinese local people is increased according to tumor grade and is an independent risk factor. TN-C mediates BCa cell malignant behavior via syndecan-4 and NF-κB signaling. Although the mechanisms through which syndecan-4 is associated with the activation of NF-κB signaling are unclear, the data presented herein provide a foundation for future investigations into the role of TN-C in BCa progression.


Assuntos
NF-kappa B/metabolismo , Transdução de Sinais/genética , Sindecana-4/metabolismo , Tenascina/metabolismo , Neoplasias da Bexiga Urinária/genética , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Humanos , Bexiga Urinária/metabolismo
6.
Neuroradiology ; 64(1): 129-140, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34379142

RESUMO

PURPOSE: The aim of the study is to explore interhemispheric homotopic functional connectivity alterations in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric lupus (NPSLE and non-NPSLE, respectively) and their potential correlations with clinical characteristics and neuropsychological performance. METHODS: Based on resting-state functional MRI (rs-fMRI) data collected from SLE patients and matched healthy controls (HCs), the voxel-mirrored homotopic connectivity (VMHC) analysis was conducted to measure functional homotopy. Subsequently, correlations between altered functional homotopy and clinical/neuropsychological data were analyzed. RESULTS: Compared with the HC group, both NPSLE and non-NPSLE groups showed attenuated homotopic connectivity in middle temporal gyrus (MTG), cuneus (CUN), middle occipital gyrus (MOG), angular gyrus (ANG), and postcentral gyrus (PoCG). NPSLE patients also exhibited decreased homotopic connectivity in inferior parietal gyrus (IPG) and middle frontal gyrus (MFG). Compared with non-NPSLE patients, NPSLE patients showed weaker interhemispheric homotopic functional connectivity in MOG. Decreased homotopic functional connectivity in PoCG, IPG, and MOG were associated with the anxiety state of SLE patients. CONCLUSIONS: Our findings revealed attenuated functional homotopy in both NPSLE and non-NPSLE groups compared to the HC group, which appeared to be more severe in patients with comorbid neuropsychiatric lupus. Interhemispheric homotopy dysconnectivity may participate in the neuropathology of anxiety symptoms in SLE.


Assuntos
Lúpus Eritematoso Sistêmico , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico por imagem , Imageamento por Ressonância Magnética
7.
Breast Cancer Res Treat ; 178(1): 35-49, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31327090

RESUMO

PURPOSE: Although survival rates for patients with localized breast cancer have increased, patients with metastatic breast cancer still have poor prognosis. Understanding key factors involved in promoting breast cancer metastasis is imperative for better treatments. In this study, we investigated the role of syndecan-1 (Sdc1) in breast cancer metastasis. METHODS: To assess the role of Sdc1 in breast cancer metastasis, we silenced Sdc1 expression in the triple-negative breast cancer human MDA-MB-231 cell line and overexpressed it in the mouse mammary carcinoma 4T1 cell line. Intracardiac injections were performed in an experimental mouse metastasis model using both cell lines. In vitro transwell blood-brain barrier (BBB) and brain section adhesion assays were utilized to specifically investigate how Sdc1 facilitates brain metastasis. A cytokine array was performed to evaluate differences in the breast cancer cell secretome when Sdc1 is silenced. RESULTS: Silencing expression of Sdc1 in breast cancer cells significantly reduced metastasis to the brain. Conversely, overexpression of Sdc1 increased metastasis to the brain. We found that silencing of Sdc1 expression had no effect on attachment of breast cancer cells to brain endothelial cells or astrocytes, but migration across the BBB was reduced as well as adhesion to the perivascular regions of the brain. Loss of Sdc1 also led to changes in breast cancer cell-secreted cytokines/chemokines, which may influence the BBB. CONCLUSIONS: Taken together, our study demonstrates a role for Sdc1 in promoting breast cancer metastasis to the brain. These findings suggest that Sdc1 supports breast cancer cell migration across the BBB through regulation of cytokines, which may modulate the BBB. Further elucidating this mechanism will allow for the development of therapeutic strategies to combat brain metastasis.


Assuntos
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Sindecana-1/genética , Sindecana-1/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Animais , Barreira Hematoencefálica/imunologia , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Movimento Celular , Citocinas/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Camundongos , Transplante de Neoplasias , Análise Serial de Tecidos , Neoplasias de Mama Triplo Negativas/genética , Regulação para Cima
8.
Arch Gynecol Obstet ; 296(6): 1145-1152, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28975405

RESUMO

AIM: Resistance to platinum-based therapeutic agents is the major contributor to epithelial ovarian cancer (EOC) mortality. There is an urgent need to better understand the underlying mechanisms. Here we investigated the role of serpins in EOC chemoresistance and related mechanisms, and found that SERPINE1 played an important role in chemoresistance in A2780cp cells. MATERIALS AND METHODS: A2780cp and A2780s cells were used in our study. Microarray screening was used to identify the gene expression change under carboplatin treatment. A cell-counting kit-8 was used to detect the sensitivity of ovarian cancer cells after treatment. The expression of SERPINE1 was silenced by siRNA. The levels of SERPINE1 and epithelial-mesenchymal transition (EMT)-related proteins were confirmed by Western blot. MassArray EpiTYPER quantitative DNA methylation analysis was introduced to evaluate the methylation of the promoter of SERPINE1. RESULTS: Microarray data showed that SERPINE1 and SERPINE2 increased most dramatically under carboplatin treatment in A2780cp cells. Carboplatin treatment could significantly increase the expression of SERPINE1 and induce the EMT process, with decreased expression of E-cadherin and increased expression of Vimentin, Snail and Twist. Knockdown of SERPINE1, but not SERPINE2, in A2780cp cells could inhibit the EMT process. We also found that hypomethylation in the promoter of SERPINE1 might result in the increased expression of SERPINE1 and subsequent EMT process in A2780cp cells. CONCLUSION: Our study suggested that SERPINE1 may be a promising therapeutic target for chemoresistance.


Assuntos
Carboplatina/farmacologia , Metilação de DNA , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Inibidor 1 de Ativador de Plasminogênio/genética , Antígenos CD , Antineoplásicos , Caderinas/metabolismo , Carboplatina/uso terapêutico , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Regiões Promotoras Genéticas , Serpina E2
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 16(12): 1226-30, 2014 Dec.
Artigo em Zh | MEDLINE | ID: mdl-25523570

RESUMO

OBJECTIVE: To investigate the pathologic bacterial distribution and their antibiotic resistance in infants aged from 1 to 3 months with lower respiratory tract infection, so as to provide instructions for clinical application of antibiotics. METHODS: Induced sputum was extracted from 622 cases of hospitalized infants aged from 1 to 3 months with lower respiratory tract infection between January 2013 and December 2013, and microbial sensitivity test was performed with agar diffusion sensitivity test. RESULTS: A total of 379 (60.9%) strains of bacteria were isolated from induced sputum in the 622 infants. The Gram-negative strains were detected in 325 strains (85.8%), and the Gram-positive strains were found in 50 strains (13.2%) in the 379 strains. The others were Fungal strains (4 strains, 1.1%). The Gram-negative bacteria included Escherichia coli (31.1%) and Klebsiella pneumoniae (18.2%), with extended-spectrum ß-lactamases (ESBLs) production of 48.3% and 52.2% respectively. The average rate of antibiotic resistance for ESBLs-producing bacteria was 53%. ESBLs-producing bacteria were highly resistant (100%) to ampicillin and cefotaxime, but sensitive to carbapenems. Staphylococcus aureus (10.0%) was the dominant bacteria in Gram-positive bacteria. A lower proportion of methicillin-resistant Staphylococcus aureus (1.8%) was observed, however the resistance rate of methicillin-resistant Staphylococcus aureus to ß-lactam antibiotics were 100%. CONCLUSIONS: Escherichia coli and Klebsiella pneumoniae are the main pathogenic bacteria causing lower respiratory tract infection in infants aged from 1 to 3 months. ESBLs-producing bacteria accounted for over 48%, and the antibiotic resistance rate were more than 53% in these infants. These results provide a basis for the first empirical clinical use of antimicrobial in infants with lower respiratory tract infection.


Assuntos
Farmacorresistência Bacteriana , Infecções Respiratórias/microbiologia , Escarro/microbiologia , Escherichia coli/isolamento & purificação , Feminino , Humanos , Lactente , Klebsiella pneumoniae/isolamento & purificação , Masculino , Infecções Respiratórias/tratamento farmacológico
10.
Science ; 384(6701): eadk5382, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38870290

RESUMO

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.


Assuntos
Proteases Dependentes de ATP , Artemisininas , Enzima de Clivagem da Cadeia Lateral do Colesterol , Proteínas Mitocondriais , Síndrome do Ovário Policístico , Animais , Feminino , Humanos , Camundongos , Ratos , Androgênios/metabolismo , Artemisininas/uso terapêutico , Artemisininas/farmacologia , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Modelos Animais de Doenças , Hiperandrogenismo/tratamento farmacológico , Hiperandrogenismo/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Ovário/efeitos dos fármacos , Ovário/metabolismo , Síndrome do Ovário Policístico/tratamento farmacológico , Proteólise , Camundongos Endogâmicos C57BL , Adulto Jovem , Adulto , Ratos Sprague-Dawley , Proteases Dependentes de ATP/genética , Proteases Dependentes de ATP/metabolismo
11.
Cureus ; 15(10): e46326, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37916260

RESUMO

Compressive postoperative seromas in the cervical spine are a rare but significant complication following cervical laminectomy and instrumented fusion. There is a paucity of cases reported in the literature, with a majority of the reported cases attributing seroma formation to the use of recombinant human bone morphogenetic protein-2 (rhBMP-2). In this article, we report four cases of compressive postoperative seroma in the absence of rhBMP-2 use and highlight similarities in their clinical presentations. We postulate that seroma formation is a significant complication of the dead space that results following posterior instrumentation in the cervical spine, with or without the use of rhBMP-2. The typical presentation is one of the gradual delayed neurological deterioration several days following the index surgery and after drain removal. Neurological deterioration can be reversed rapidly with early recognition and drainage of the seroma.

12.
Quant Imaging Med Surg ; 13(10): 6952-6964, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37869356

RESUMO

Background: Transperineal ultrasound (TPUS) is a vital examination method for diagnosing pelvic floor diseases. However, the quality of TPUS largely relies on the operator's experience, and there is a lack of studies on the evaluation of TPUS quality. Therefore, the objective of this study was to assess the quality of TPUS examinations in Chinese tertiary medical centers. Methods: This multicenter study conducted in 44 Chinese tertiary medical centers recruited postpartum women between September 2020 and September 2021. All participants underwent a standardized inquiry and TPUS examination. The participating centers were required to submit 5 parts of ultrasound data to the National Ultrasound Quality Control Center: 2-dimensional images at rest, 2-dimensional images at strain; 4-dimensional images of the levator ani hiatus; 4-dimensional images of the levator ani muscle; and 4-dimensional images of the anal sphincter. Quality assessment was performed by 2 experts with more than 5 years of experience in TPUS, and the reasons for nonqualification were stated. Results: In this study, 31 hospitals that were distributed across 20 provinces in China were included, submitting 2,251 cases in total. The overall qualified rate ranged from 12.00% to 86.92%. In each part, the qualified rate of 2-dimensional images at rest, 2-dimensional images at straining, levator ani hiatus, levator ani muscle, and anal sphincter was 94.27% (2,122/2,251), 78.54% (1,768/2,251), 85.52% (1,925/2,251), 93.03% (2,094/2,251), and 88.09% (1,983/2,251), respectively. Most of the nonqualified images belonged to 2-dimensional images at strain, and the errors in image acquisition (221/483, 45.76%) and measurement (262/483, 54.24%) were the main reasons for nonqualification. For levator ani hiatus images, error in image acquisition (275/326, 84.36%) was the main reason for nonqualification. Reconstruction error was the most common reason for nonqualification for levator ani muscle (133/157, 84.71%) and anal sphincter images (133/268, 49.63%). Conclusions: This multicenter study assessed the quality of TPUS in tertiary medical centers in China and identified the common reasons for nonqualification in each part. These findings can aid in forming the basis for quality control management and training for TPUS.

13.
Front Public Health ; 10: 1040704, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36530731

RESUMO

Background: To provide reliable evidence to exercise rehabilitation therapists and clinicians, we compared and analyzed the effects of different exercise modalities on cardiopulmonary function in hemodialysis patients using Bayesian network meta-analysis. Methods: PubMed, OVID, Web of Science, Cochrane Library, Embase, Scopus, CINAHL, SPORT Discus, SinoMed, CNKI, Wanfang, and VIP were searched from inception to July 20, 2022. We included randomized controlled trials comparing 12 exercise modalities to improve cardiorespiratory fitness in hemodialysis patients. All statistical analysis was performed using STATA and R. Result: A total of 82 randomized controlled trials involving 4146 maintenance hemodialysis patients were included in this study. The pair-wise meta-analysis showed that all exercise modalities had a positive effect on all indicators of cardiorespiratory capacity. The network meta-analysis demonstrated that Blood flow restriction training (BFRT), Cycle exercise (CE), Inspiratory muscle training (IMT), Combined aerobic and resistance training (CT), and Aerobic training (AT) were significantly better than usual care for 6-min walkability; Medium intensity continuous training (MICT), CT, CE, and AT were considerably better than usual care for VO2Peak; body and mind training (MBT) and CT significantly improved SBP compared to usual care; and only MBT was significantly better than usual care for DBP. Both the two-dimensional plot and the radar plot demonstrated that CT had the best combined-effect on each index of cardiorespiratory fitness. Subgroup and sensitivity analyses demonstrated the robustness of the results. The evidence was mainly "low" to "very low" for this network meta-analysis. Conclusion: There is no one exercise that can achieve the best effect on all of the outcomes. The benefits of MBT in decreasing arterial blood pressure are unsurpassed by other exercise methods. The intervention effect of the CT is better and more stable. Electrical muscle stimulation training (MEST) can be employed in individuals who do not wish to exercise actively but may cause an increase in blood pressure. On the basis of the characteristics of different exercise types, guidelines developers, clinicians, and patients may employ them appropriately. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails.


Assuntos
Terapia por Exercício , Exercício Físico , Humanos , Metanálise em Rede , Teorema de Bayes , Terapia por Exercício/métodos , Diálise Renal , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
World J Clin Cases ; 9(16): 3979-3987, 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34141756

RESUMO

BACKGROUND: Obturator dislocation is a rare type of hip dislocation, accounting for about 2%-5% of all hip dislocations. The occurrence of old unreduced obturator dislocation is even more infrequent, with only 17 cases reported in nine studies, most of which were from the 1950s to 1980s in developing countries. CASE SUMMARY: A 38-year-old woman from Hunan Province, China presented with stiffness of the left hip in abduction, flexion, and external rotation after falling from a 2-meter-tall tree onto her left knee 1.5 mo prior. Pelvic radiograph and computed tomography revealed obturator dislocation of the left hip accompanied by impaction fracture at the superolateral aspect of the left femoral head without associated acetabulum fracture. Open reduction was performed, resulting in restoration of the concentric alignment of the left hip. After surgery, 6-wk skin traction was applied and the patient was kept in bed for an additional 2 wk. At 3 mo after surgery, the patient reported experiencing some pain, which did not affect the function of the affected limb, and some movement restriction but no abduction deformity or claudication was present. An X-ray showed that the left hip was homocentric, and there was no sign of posttraumatic arthritis or avascular necrosis. CONCLUSION: Open reduction may be an effective treatment strategy for the rare condition of old unreduced obturator dislocation with short neglect time.

15.
Front Endocrinol (Lausanne) ; 12: 646720, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34322090

RESUMO

We have previously shown that biochanin A exhibits neuroprotective properties in the context of cerebral ischemia/reperfusion (I/R) injury. The mechanistic basis for such properties, however, remains poorly understood. This study was therefore designed to explore the manner whereby biochanin A controls endoplasmic reticulum (ER) stress, apoptosis, and inflammation within fetal rat primary cortical neurons in response to oxygen-glucose deprivation/reoxygenation (OGD/R) injury, and in a rat model of middle cerebral artery occlusion and reperfusion (MCAO/R) injury. For the OGD/R in vitro model system, cells were evaluated after a 2 h OGD following a 24 h reoxygenation period, whereas in vivo neurological deficits were evaluated following 2 h of ischemia and 24 h of reperfusion. The expression of proteins associated with apoptosis, ER stress (ERS), and p38 MAPK phosphorylation was evaluated in these samples. Rats treated with biochanin A exhibited reduced neurological deficits relative to control rats following MCAO/R injury. Additionally, GRP78 and CHOP levels rose following I/R modeling both in vitro and in vivo, whereas biochanin A treatment was associated with reductions in CHOP levels but further increases in GRP78 levels. In addition, OGD/R or MCAO/R were associated with markedly enhanced p38 MAPK phosphorylation that was alleviated by biochanin A treatment. Similarly, OGD/R or MCAO/R injury resulted in increases in caspase-3, caspase-12, and Bax levels as well as decreases in Bcl-2 levels, whereas biochanin A treatment was sufficient to reverse these phenotypes. Together, these findings thus demonstrate that biochanin A can alleviate cerebral I/R-induced damage at least in part via suppressing apoptosis, ER stress, and p38 MAPK signaling, thereby serving as a potent neuroprotective agent.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Genisteína/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Apoptose , Encéfalo/metabolismo , Proliferação de Células , Sobrevivência Celular , Feminino , Genisteína/química , Glucose/metabolismo , Humanos , Técnicas In Vitro , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Oxigênio/metabolismo , Fosforilação , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
16.
World J Clin Cases ; 8(12): 2634-2640, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32607343

RESUMO

BACKGROUND: Acetabular anterior wall fracture with preservation of the pelvic brim is extremely rare. It is different from anterior wall fracture classified by Judet and Letournel. Few studies have reported cases treated by open reduction and internal fixation via the Smith-Petersen or iliofemoral approach. CASE SUMMARY: We report a 48-year-old Chinese woman who had difficulty moving her right hip from abduction and external rotation after falling from 3 m. Pelvic radiograph and three-dimensional reconstruction of computed tomography revealed acetabular anterior wall fractures combined with fractures of the anterior inferior iliac spine and the iliac wing but not involving the pelvic brim. First, the patient underwent interim management by closed reduction of the hip dislocation and skin traction for 6 d. Then, we used a modified pararectus approach for treatment to fix the acetabular fractures with a reconstruction plate and nonlocking T-shape plate. At the 9-mo follow-up, the patient could walk painlessly without necrosis of the femoral head or heterotopic ossification, and the X-rays and computed tomography scan reconstructions showed good bone union. CONCLUSION: The modified pararectus approach described here can facilitate exposure, reduction, and osteosynthesis for atypical acetabular fracture with less invasiveness.

17.
RSC Adv ; 9(36): 20528-20535, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35515569

RESUMO

A small crystal NaY zeolite with a high SiO2/Al2O3 ratio was successfully synthesized with seeding and without organic template, and the effects of the silicon source, aging time and Na2O seeding content on the crystal size of NaY zeolite were investigated. The synthesized samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-Transform Infrared (FT-IR) spectroscopy and N2 adsorption-desorption. The results showed that the silicon source used to prepare seeding had a great effect on the crystal size of NaY zeolite, NaY zeolite with average size of 100 nm and SiO2/Al2O3 ratio of 5.42 was obtained by using the seeding prepared with silica sol. Moreover, the crystal size of NaY zeolite decreased with an extension of the aging time and an increase of the Na2O content of seeding. The catalytic performance of small crystal Y zeolite was evaluated in the hydrocracking of vacuum gas oil (VGO), the catalyst with smaller crystal Y zeolite presented higher VGO conversion and middle distillates selectivity than those with larger ones due to its higher surface area and more amount of mesoporous.

18.
Biomed Pharmacother ; 116: 108962, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31103826

RESUMO

Currently, exploring tumor-promoting or tumor-suppressing factors is a promising approach to find new targets for cancer therapy. In this context, through analysis of GSE datasets (GSE3189 and GSE112509), stress induced phosphoprotein 1 (STIP1) was found to be overexpressed in melanoma tissues compared to benign skin nevi and normal skin tissues, respectively. High expression of STIP1 protein was further confirmed in our melanoma specimens. The survival data of skin cutaneous melanoma in TCGA database indicated that high STIP1 level predicted poor clinical outcomes of patients. Functionally, STIP1 knockdown significantly inhibited cell proliferation, migration and invasion, and induced apoptosis of A2058 cells in vitro. Additionally, STIP1 silencing prominently reduced lung metastasis of melanoma cells in vivo. Whereas, STIP1 overexpression facilitated the growth and metastasis of M14 cells. Intriguingly, STIP1 overexpression markedly increased Janus kinase 2 (JAK2) expression and activated JAK2/signal transducer and activator of transcription 3 (STAT3) pathway in M14 cells, while knockdown of STIP1 blocked JAK2/STAT3 pathway in A2058 cells. Importantly, JAK2 knockdown reversed STIP1-induced melanoma cell proliferation, migration and invasion. Thus, we revealed a novel mechanism underlying STIP1-induced melanoma progression by regulating JAK2/STAT3 pathway. This study might provide a new insight to understand the pathogenesis of melanoma and possibly contributed to development of therapeutic approaches for melanoma.


Assuntos
Proteínas de Choque Térmico/metabolismo , Janus Quinase 2/metabolismo , Melanoma/patologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Neoplasias Cutâneas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma/genética , Metástase Neoplásica , Oncogenes , Prognóstico , Neoplasias Cutâneas/genética , Regulação para Cima/genética
19.
Sci Rep ; 9(1): 268, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30670727

RESUMO

Quantum coherence and quantum correlations lie in the center of quantum information science, since they both are considered as fundamental reasons for significant features of quantum mechanics different from classical mechanics. We present a group of complementary relations for quantum coherence and quantum correlations; specifically, we focus on thermal discord and conditional information in scenarios of multiple measurements. We show that the summation of quantum coherence quantified in different bases has a lower bound, resulting from entropic uncertainty relations with multiple measurements. Similar results are also obtained for thermal discord and for post-measurement conditional information with multiple measurements in a multipartite system. These results indicate the general applications of the uncertainty principle to various concepts of quantum information.

20.
Anal Cell Pathol (Amst) ; 2019: 9192516, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31183318

RESUMO

Breast cancer is one of the most common forms of cancer affecting women in the United States, second only to skin cancers. Although treatments have been developed to combat primary breast cancer, metastasis remains a leading cause of death. An early step of metastasis is cancer cell invasion through the basement membrane. However, this process is not yet well understood. AG73, a synthetic laminin-α1 chain peptide, plays an important role in cell adhesion and has previously been linked to migration, invasion, and metastasis. Thus, we aimed to identify the binding partner of AG73 on breast cancer cells that could mediate cancer progression. We performed adhesion assays using MCF10A, T47D, SUM1315, and MDA-231 breast cell lines and found that AG73 binds to syndecans (Sdcs) 1, 2, and 4. This interaction was inhibited when we silenced Sdcs 1 and/or 4 in MDA-231 cells, indicating the importance of these receptors in this relationship. Through actin staining, we found that silencing of Sdc 1, 2, and 4 expression in MDA-231 cells exhibits a decrease in the length and number of filopodia bound to AG73. Expression of mouse Sdcs 1, 2, and 4 in MDA-231 cells provides rescue in filopodia, and overexpression of Sdcs 1 and 2 leads to increased filopodium length and number. Our findings demonstrate an intrinsic interaction between AG73 in the tumor environment and the Sdcs on breast cancer cells in supporting tumor cell adhesion and invasion through filopodia, an important step in cancer metastasis.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Laminina/metabolismo , Sindecana-1/metabolismo , Sindecana-2/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Invasividade Neoplásica , Metástase Neoplásica , Peptídeos/metabolismo , Ligação Proteica
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