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Hot-carrier transistors are a class of devices that leverage the excess kinetic energy of carriers. Unlike regular transistors, which rely on steady-state carrier transport, hot-carrier transistors modulate carriers to high-energy states, resulting in enhanced device speed and functionality. These characteristics are essential for applications that demand rapid switching and high-frequency operations, such as advanced telecommunications and cutting-edge computing technologies1-5. However, the traditional mechanisms of hot-carrier generation are either carrier injection6-11 or acceleration12,13, which limit device performance in terms of power consumption and negative differential resistance14-17. Mixed-dimensional devices, which combine bulk and low-dimensional materials, can offer different mechanisms for hot-carrier generation by leveraging the diverse potential barriers formed by energy-band combinations18-21. Here we report a hot-emitter transistor based on double mixed-dimensional graphene/germanium Schottky junctions that uses stimulated emission of heated carriers to achieve a subthreshold swing lower than 1 millivolt per decade beyond the Boltzmann limit and a negative differential resistance with a peak-to-valley current ratio greater than 100 at room temperature. Multi-valued logic with a high inverter gain and reconfigurable logic states are further demonstrated. This work reports a multifunctional hot-emitter transistor with significant potential for low-power and negative-differential-resistance applications, marking a promising advancement for the post-Moore era.
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Temperatura Alta , Transistores Eletrônicos , Grafite/químicaRESUMO
Advancing spatially resolved transcriptomics (ST) technologies help biologists comprehensively understand organ function and tissue microenvironment. Accurate spatial domain identification is the foundation for delineating genome heterogeneity and cellular interaction. Motivated by this perspective, a graph deep learning (GDL) based spatial clustering approach is constructed in this paper. First, the deep graph infomax module embedded with residual gated graph convolutional neural network is leveraged to address the gene expression profiles and spatial positions in ST. Then, the Bayesian Gaussian mixture model is applied to handle the latent embeddings to generate spatial domains. Designed experiments certify that the presented method is superior to other state-of-the-art GDL-enabled techniques on multiple ST datasets. The codes and dataset used in this manuscript are summarized at https://github.com/narutoten520/SCGDL.
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Aprendizado Profundo , Transcriptoma , Teorema de Bayes , Perfilação da Expressão Gênica , Comunicação CelularRESUMO
OBJECTIVE: To evaluate the effectiveness of botulinum toxin A (BTX-A) in the treatment of hemiplegic shoulder pain. DATA SOURCES: PubMed, EMBASE, Elsevier, Springer, Cochrane Library, Physiotherapy Evidence Database, CNKI, and VIP were researched from the earliest records to September 1, 2020. STUDY SELECTION: Randomized controlled trials that compared shoulder BTX-A injections vs a control intervention in patients with a history of hemiplegic shoulder pain after stroke were selected. Among the 620 records screened, 9 trials with 301 eligible patients were included. DATA EXTRACTION: Outcome data were pooled according to follow-up intervals (1, 2, 4, and 12 wk). The primary evaluation indices were pain reduction (visual analog scale [VAS] score) and range of motion (ROM) improvement. The second evaluation indices were upper limb functional improvement, spasticity improvement, and incidence of adverse events. Cochrane risk-of-bias was used to assess the methodological quality of studies independently by 2 evaluators. DATA SYNTHESIS: Meta-analysis revealed a statistically significant decrease in the VAS score in the BTX group vs the control group at 1, 4, and 12 weeks postinjection (wk 1: standardized mean difference [SMD], 0.91; 95% confidence interval [CI], 0.27 to 1.54; wk 4: SMD, 1.63; 95% CI, 0.76 to 2.51; wk 12: SMD, 1.96; 95% CI, 1.44 to 2.47). Furthermore, the meta-analysis demonstrated a statistically significant increase in abduction at 1, 4, and 12 weeks postinjection (wk 1: SMD, 3.71; 95% CI, 0 to 7.41; wk 4: SMD, 8.8; 95% CI, 2.22 to 15.37; wk 12: SMD, 19.59; 95% CI, 9.05 to 30.13) and external rotation at 1, 2, 4 weeks postinjection (wk 1: SMD, 5.67; 95% CI, 0.88 to 10.47; wk 2: SMD, 9.62; 95% CI, 5.57 to 13; wk 4: SMD, 6.89; 95% CI, 2.45 to 11.33) in the BTX group. CONCLUSIONS: BTX-A injection provided greater analgesic effects and increased shoulder abduction and external rotation ROM compared with steroid or placebo injection for the treatment of HSP.
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Toxinas Botulínicas Tipo A/uso terapêutico , Hemiplegia/tratamento farmacológico , Espasticidade Muscular/tratamento farmacológico , Dor de Ombro/tratamento farmacológico , Humanos , Injeções Intramusculares , Fármacos Neuromusculares/uso terapêutico , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Amplitude de Movimento ArticularRESUMO
OBJECTIVE: To investigate the effect and mechanism of static progressive stretching (SPS) in different durations on traumatic knee contracture in rats. METHODS: Seventy male Wistar rats were randomly divided into three groups, including surgical modeling group ( n=50), control group (CON, no surgery, no treatment, n=10) and trauma without immobilization group (TRA, no treatment, n=10). The knee contracture model was established, and 50 surgical modeling rats were randomly divided into five groups including static progressive stretching treatment for 20 minutes group (S20 min, n=10), treatment for 30 minutes group (S30 min, n=10), treatment for 40 minutes group (S40 min, n=10), untreatment group (UNT, no SPS, n=10) and modeling group (MOD, n=10, euthanized after immobilization for histological staining and Western blot). Individuals in the S20 min, S30 min, and S40 min groups were anesthetized and submitted to SPS. One treatment session took place every other day. A total of 8 sessions were given till the final treatment session on the day 16. On the day 0, 8, and 16 of intervention, the range of joint motion (ROM) and gait analysis were measured and compared. After the ROM measurements and gait analysis, the rats were euthanized on the day 16 and the samples were stained with HE and Masson methods. The changes of pathological organization were observed. Western blot was used to detect the expressions of transforming growth factor-ß1 (TGF-ß1) and interleukin-6 (IL-6). RESULTS: â ROMï¼the ROM of S30 min group recovered similar to that of the S20 min and S40 min groups after 8 days of treatment ( P>0.05), and was the best among all the surgical modeling groups after 16 d of treatment ( P<0.05). The ROM of S20 min, S30 min and S40 min groups significantly improved on the day 8 and day 16 comparing with that on day 0 ( P<0.01). â¡ Gait analysis: the stands in the S30min group improved best on the day 8 and day 16 ( P<0.05) , and better than that on day 0 ( P<0.05). The stride length of the S30 min group progressed similar to that of the S40 min group on the day 8 ( P>0.05), and there was no difference among three groups on the day 16 ( P>0.05). The stride length of the S30 min group appeared to recover more quickly on the day 8 ( P<0.05), and those of S20 min and UNT groups recovered significantly on the day 16 ( P<0.05). In addition, the swings in the S30 min group improved best ( P<0.05), and it appeared to recover better on the day 16 ( P<0.05). There was no statistical difference in terms of the swing speed among the four surgical modeling groups on the day 8 ( P>0.05). The swing speed of the S30min group increased most than those of the other three groups ( P<0.05), and it was much better on the day 8 and day 16 comparing with that on the day 0 ( P<0.05 ). ⢠HE and Masson staining: the fibrosis and inflammation of the S30min group were significantly suppressed comparing to the other groups on the day 16. ⣠Western blot: The protein expression levels of TGF-ß1 and IL-6 were significantly lower than those in the other intervention groups including the S20 min, S40 min and UNT groups on the day 16 ( P<0.05). CONCLUSION: Static progressive stretching treatment for 30 min could significantly improve the traumatic knee contracture in rats. The mechanism may be that the SPS decreased the expressions of TGF-ß1 and IL-6, reduced the adhesion and inflammation of joint capsule. Therefore it relieved the pain and increased the joint mobility by reconstructing the structure of the capsule and suppressing the fibrotic changes.
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Contratura , Articulação do Joelho/fisiopatologia , Exercícios de Alongamento Muscular , Animais , Fenômenos Biomecânicos , Contratura/terapia , Interleucina-6/metabolismo , Cápsula Articular , Masculino , Amplitude de Movimento Articular , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta1/metabolismoRESUMO
BACKGROUND There has been no published report assessing the mechanical properties of a repaired Achilles tendon after surgery using shear wave elastography (SWE). The aim of this study was to investigate the changes in mechanical properties of the healing Achilles tendon after surgical repair of a tendon rupture using ultrasound SWE and how these changes correlate with tendon function. MATERIAL AND METHODS Twenty-six patients who underwent surgical repair for Achilles tendon rupture were examined with ultrasound SWE coupled with a linear array transducer (4-15 MHz). The elasticity values of the repaired Achilles tendon in a longitudinal view were measured at 12, 24, and 48 weeks postoperatively. Functional outcomes were assessed with the American Orthopedic Foot and Ankle Society (AOFAS) rating system at 12, 24, and 48 weeks postoperatively. General linear regression analysis and correlation coefficients were used to analyze the relationship between elasticity and the AOFAS score. RESULTS There were significant differences with respect to the mean elasticity values and functional scores of the repaired Achilles tendon at 12, 24, and 48 weeks postoperatively (all P<0.05). Tendon function was positively correlated with the elasticity of the repaired Achilles tendon (P=0.0003). CONCLUSIONS Our findings suggest that SWE can provide biomechanical information for evaluating the mechanical properties of healing Achilles tendon and predict Achilles tendon function.
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Tendão do Calcâneo/lesões , Tendão do Calcâneo/fisiopatologia , Traumatismos dos Tendões/fisiopatologia , Cicatrização/fisiologia , Tendão do Calcâneo/diagnóstico por imagem , Tendão do Calcâneo/cirurgia , Adulto , Idoso , Módulo de Elasticidade , Técnicas de Imagem por Elasticidade/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/métodos , Procedimentos de Cirurgia Plástica/métodos , Ruptura , Traumatismos dos Tendões/diagnóstico por imagem , Traumatismos dos Tendões/cirurgia , Resultado do Tratamento , Ultrassom , Ultrassonografia/métodosRESUMO
BACKGROUND: To set up a method for measuring radiographic displacement of unstable pelvic ring fractures based on standardized X-ray images and then test its reliability and validity using a software-based measurement technique. METHODS: Twenty-five patients that were diagnosed as AO/OTA type B or C pelvic fractures with unilateral pelvis fractured and dislocated were eligible for inclusion by a review of medical records in our clinical centre. Based on the input pelvic preoperative CT data, the standardized X-ray images, including inlet, outlet, and anterior-posterior (AP) radiographs, were simulated using Armira software (Visage Imaging GmbH, Berlin, Germany). After representative anatomic landmarks were marked on the standardized X-ray images, the 2-dimensional (2D) coordinates of these points could be revealed in Digimizer software (Model: Mitutoyo Corp., Tokyo, Japan). Subsequently, we developed a formula that indicated the translational and rotational displacement patterns of the injured hemipelvis. Five separate observers calculated the displacement outcomes using the established formula and determined the rotational patterns using a 3D-CT model based on their overall impression. We performed 3D reconstruction of all the fractured pelvises using Mimics (Materialise, Haasrode, Belgium) and determined the translational and rotational displacement using 3-matic suite. The interobserver reliability of the new method was assessed by comparing the continuous measure and categorical outcomes using intraclass correlation coefficient (ICC) and kappa statistic, respectively. RESULT: The interobserver reliability of the new method for translational and rotational measurement was high, with both ICCs above 0.9. Rotational outcome assessed by the new method was the same as that concluded by 3-matic software. The agreement for rotational outcome among orthopaedic surgeons based on overall impression was poor (kappa statistic, 0.250 to 0.426). Compared with the 3D reconstruction outcome, the interobserver reliability of the formula method for translational and rotational measures was perfect with both ICCs more than 0.9. CONCLUSIONS: The new method for measuring displacement using a formula was reliable, and could minimise the measurement errors and maximise the precision of pelvic fracture description. Furthermore, this study was useful for standardising the operative plan and establishing a theoretical basis for robot-assisted pelvic fracture surgery based on 2-D radiographs.
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Fraturas Ósseas/diagnóstico por imagem , Luxações Articulares/diagnóstico , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/lesões , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Adulto , Algoritmos , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Reprodutibilidade dos Testes , SoftwareRESUMO
Osteoarthritis (OA) is the most common type of degenerative joint disease which affects 7% of the global population and more than 500 million people worldwide. One research frontier is the development of hydrogels for OA treatment, which operate either as functional scaffolds of tissue engineering or as delivery vehicles of functional additives. Both approaches address the big challenge: establishing stable integration of such delivery systems or implants. Adhesive hydrogels provide possible solutions to this challenge. However, few studies have described the current advances in using adhesive hydrogel for OA treatment. This review summarizes the commonly used hydrogels with their adhesion mechanisms and components. Additionally, recognizing that OA is a complex disease involving different biological mechanisms, the bioactive therapeutic strategies are also presented. By presenting the adhesive hydrogels in an interdisciplinary way, including both the fields of chemistry and biology, this review will attempt to provide a comprehensive insight for designing novel bioadhesive systems for OA therapy.
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Hidrogéis , Osteoartrite , Humanos , Hidrogéis/uso terapêutico , Adesivos/uso terapêutico , Engenharia Tecidual , Osteoartrite/terapiaRESUMO
OBJECTIVE: The purpose of this study was to investigate the effects of different durations of static progressive stretching (SPS) on posttraumatic knee contracture in rats, including range of motion (ROM), gait analysis, myofibroblast proliferation, and collagen regulation. METHODS: The posttraumatic knee contracture model was established, and male Wistar rats were randomly divided into the 20-minute SPS treatment, 30-minute SPS treatment (S30), 40-minute SPS treatment, untreated, immobilization, and control groups. At Week 1, 2, and 4 of treatment intervention, joint ROM and gait were measured and compared. Knee joint samples stained with hematoxylin and eosin and Masson trichrome were used to observe alterations in pathological structures. Collagen density and cell numbers in the posterior joint capsule were used to assess joint capsule fibrosis and inflammation. Immunohistochemistry was used to detect type I collagen and α-smooth muscle actin expression. RESULTS: The S30 group improved the most; ROM, stance, mean intensity, print area, and stride length were 115 (SD = 5) degrees, 0.423 (SD = 0.074) seconds, 156.020 (SD = 7.952), 2.116 (SD = 0.078) cm2, and 11.758 (SD = 0.548) cm, respectively. The numbers of myofibroblasts, fibroblasts, and inflammatory cells decreased, and collagen proliferation was significantly suppressed in the S30 group compared with the other groups. CONCLUSION: S30 significantly improved posttraumatic knee contracture in rats, with reduced type I collagen and α-smooth muscle actin expression, decreased the numbers of myofibroblasts and inflammatory cells, suppressed fibrotic and inflammatory changes in the joint capsule, and increased joint mobility. This study provided basic evidence for an optimal standard-of-care treatment approach for posttraumatic knee joint contracture in rats, which may have significance for humans.
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Contratura , Luxações Articulares , Actinas/metabolismo , Actinas/farmacologia , Animais , Colágeno , Colágeno Tipo I/metabolismo , Colágeno Tipo I/farmacologia , Contratura/terapia , Modelos Animais de Doenças , Fibrose , Humanos , Articulação do Joelho , Masculino , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Amplitude de Movimento Articular , Ratos , Ratos WistarRESUMO
The relationship between hemiplegic shoulder pain (HSP) and subluxation is unclear. This study aimed to determine the differences of magnetic resonance imaging (MRI) findings in HSP patients with or without subluxation after stroke, and to analyze the etiology of shoulder pain. This retrospective study included 53 patients with HSP after stroke from September 2013 to February 2020. Patients underwent MRI of the shoulder because of shoulder pain. Clinical characteristics, including age, sex, stroke duration, body mass index, stroke type, visual analog scale score, Brunnstrom stage, and MRI arthrography findings of the affected shoulder, were recorded. Patients were classified into the glenohumeral subluxation (GHS) group (n = 27) or non-glenohumeral subluxation (nGHS) group (n = 26). We found that patients with HSP may be prone to bursa effusion, rotator cuff injury, ligament injury, and cartilage injury, even though there was no significant difference between the GHS and nGHS groups. MRI revealed 14 cases of long bicipital tendon-glenoid labrum injury (51.8%) in the GHS group and 6 cases (23.1%) in the nGHS group (p = 0.030). We also found 10 cases (37%) of glenoid labrum injury in the GHS group and 2 cases (7.7%) in the nGHS group (p = 0.026). Eight cases (29.6%) and 1 case (3.8%) of bone marrow edema were found in the GHS and nGHS groups, respectively (p = 0.033). Compared with painful hemiplegic shoulder patients without subluxation, patients with subluxation may be more susceptible to some injuries, such as long bicipital tendon-glenoid labrum injury, glenoid labrum injury, and bone marrow edema. During rehabilitation, physicians need to pay attention to these injuries.
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The objective of this study was to investigate whether brain volume changes occur in patients with chronic ankle instability (CAI) using voxel-based morphometry and assessing correlations with clinical tests. Structural magnetic resonance imaging data were prospectively acquired in 24 patients with CAI and 34 healthy controls. CAI symptoms and pain intensity were assessed using the Foot and Ankle Ability Measure (FAAM), Cumberland Ankle Instability Tool (CAIT), American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and visual analog scale (VAS). The gray matter volume (GMV) of each voxel was compared between the two groups while controlling for age, sex, weight, and education level. Correlation analysis was performed to identify associations between abnormal GMV regions and the FAAM score, AOFAS score, VAS score, disease duration, and body mass index. Patients with CAI exhibited reduced GMV in the right precentral and postcentral areas, right parahippocampal area, left thalamus, left parahippocampal area, and left postcentral area compared to that of healthy controls. Furthermore, the right parahippocampal (r = 0.642, p = 0.001), left parahippocampal (r = 0.486, p = 0.016), and left postcentral areas (r = 0.521, p = 0.009) were positively correlated with disease duration. The left thalamus was positively correlated with the CAIT score and FAAM activities of daily living score (r = 0.463, p = 0.023 and r = 0.561, p = 0.004, respectively). A significant positive correlation was found between the local GMV of the right and left parahippocampal areas (r = 0.487, p = 0.016 and r = 0.763, p < 0.001, respectively) and the AOFAS score. Neural plasticity may occur in the precentral and postcentral areas, parahippocampal area, and thalamus in patients with CAI. The patterns of structural reorganization in patients with CAI may provide useful information on the neuropathological mechanisms of CAI.
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CD4(+)CD25(+) regulatory T cells (Treg) play the critical role in maintenance of peripheral immune tolerance. However, the numbers of naturally occurring Treg (nTreg) that can be isolated from periphery are far too small to be clinically effective. The isolation and expansion of nTreg for treatment of autoimmune diseases encounter great difficulties. Whether autoantigen-specific Treg could be converted from CD4(+)CD25(-) T cells in patients with autoimmune diseases has not been reported. Here, we demonstrated that platelet glycoprotein (GP)-specific induced Treg (GP-iTreg) could be generated de novo from nonregulatory CD4(+)CD25(-)CD45RA(+) cells in patients with idiopathic thrombocytopenic purpura and induced both antigen-specific and linked suppression. GP-iTreg mediated regulatory effects via modulating the T cell-stimulatory capacity of dendritic cells. By investigating the gene expression profile of iTreg-modulated dendritic cells, we provided a genome-wide assessment of the changes induced by antigen-specific iTreg and identified that the Toll-like receptor, Notch and transforming growth factor-beta signaling pathways were related to the GP-specific tolerance, with the Toll-like receptor pathway being dominant. The findings in patients with idiopathic thrombocytopenic purpura will facilitate our understanding of the mechanisms of induction and maintenance of autoantigen-specific tolerance and highlight the considerable potential of antigen-specific iTreg for targeted immunotherapy in human auto-immune diseases.
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Plaquetas/imunologia , Linfócitos T CD4-Positivos/imunologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Ativação Linfocitária/imunologia , Púrpura Trombocitopênica Idiopática/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Células Cultivadas , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Células Dendríticas/fisiologia , Fatores de Transcrição Forkhead/genética , Perfilação da Expressão Gênica , Humanos , Antígenos Comuns de Leucócito/metabolismo , Ativação Linfocitária/genética , Análise de Sequência com Séries de Oligonucleotídeos , Glicoproteínas da Membrana de Plaquetas/imunologia , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Idiopática/metabolismo , Púrpura Trombocitopênica Idiopática/patologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologiaRESUMO
INTRODUCTION: Symptomatic juvenile idiopathic arthritis (sJIA) is an autoinflammatory disease, and monocytes/macrophages play an important role. However, which macrophage subtype plays a major role in different stages of sJIA is still unclear. This study aimed to explore macrophage subtypes in different stages of sJIA. METHODS: Twenty-two children with sJIA who were followed up at Shanghai Children's Hospital from January 2018 to December 2020 were enrolled in this study. sJIA children were divided into an activity group (n = 12) and an inactivity group (n = 10). In the activity group, subjects with newly diagnosed sJIA and untreated were included; in the inactivity group, subjects with inactive sJIA meeting the 2011 ACR criteria for sJIA were recruited. Ten children with orthostatic proteinuria served as controls. Peripheral blood was collected. Flow cytometry was performed to detect macrophage subtypes: M1 (CD14+CD86+CD80+), M2a (CD14+CD206+CD301+), M2b (CD14+CD206+CD86+) and M2c (CD14+CD206+CD163+), and the contents of cytokines were also examined, including interleukins (IL) (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 and IL-17), interferon-α, interferon-γ, and tumor necrosis-α. RESULTS: M1 marker CD80 and M2 marker CD163, CD301 were highly expressed in children with active sJIA. The majority of macrophages were M1 and M2a in the activity group (P < 0.05). In the inactivity group, M2 tended to polarize into M2b and M2c (P < 0.05). IL-6 significantly increased in the activity group (P < 0.05), while IL-10, IL-4 and IL-17 markedly increased in the inactivity group (P < 0.05). CONCLUSIONS: In the active sJIA, M1 activation promotes inflammation, while M2a rapidly responds to inhibit inflammation; in the inactive sJIA, M2b and M2c play a major role in inhibiting inflammation.
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The objective of this bibliometric review was to identify the volume, breadth, and characteristics of clinical studies evaluating Tai Chi published between January 2010 and January 2020. Five English and four Chinese language databases were searched. Following independent screening, 1018 eligible publications representing 987 studies were identified, which was a three-fold increase from the previous decade. Most common were randomized controlled trials (548/987, 55.5 %), followed by systematic reviews (157/987, 15.9 %), non-randomized controlled clinical studies (152/987, 15.4 %), case series (127/987, 12.9 %) and case reports (3/987, 0.3 %) that were conducted in China (730/987, 74.0 %), followed by the United States of America (123/987, 12.5 %) and South Korea (20/987, 2.0 %). Study participants were mostly in the adult (55.2 %) and/or older adult (72.0 %) age groups. The top ten diseases/conditions were hypertension, chronic obstructive pulmonary disease, diabetes, knee osteoarthritis, heart failure, depression, osteoporosis/osteopenia, breast cancer, coronary heart disease and insomnia. A quarter of the studies enrolled healthy participants to evaluate the effects of Tai Chi on health promotion/preservation, balance/falls, and physiological/biomechanical outcomes. Yang style Tai Chi was the most popular, followed by Chen and Sun style. Tai Chi was mostly commonly delivered face-to-face by a Tai Chi instructor in group settings for 60 min, three times a week, for 12 weeks. Most studies (93.8 %) reported at least one outcome in favor of Tai Chi. Adverse events were underreported (7.2 %). Over half fell short of expected intervention reporting standards, signalling the need for Tai Chi extensions to existing guidelines.
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Osteoartrite do Joelho , Doença Pulmonar Obstrutiva Crônica , Tai Chi Chuan , Acidentes por Quedas , Idoso , Bibliometria , HumanosRESUMO
Joint contracture is one of the common musculoskeletal disorders. It has seriously disturbed patients' activities of daily living in various aspects. The pathogenesis of it is eager to explore to distinct degree. Nowadays the thickeness and fibrosis of joint capsular is redarded as the major reason to joint contracture. It is reported that excessive fibroblasts and myofibroblasts activity, collagen hyperplasia, and extracellular matrix (ECM) deposition in these fibrotic condtions lead to the contracture. In addition, upregulators of myofibroblast and collagen synthesis, transforming growth factor-beta 1 (TGF-ß1), and connective tissue growth factor (CTGF) were shown to be increased. Altered levels of cytokines were also thought to play a role in this process as elevated levelsof tumor necrosis factor-α(TNF-α), matrix metalloproteinases(MMPs) and abnormal distribution tissue inhibitors of MMPs(TIMPs) were demonstrated in contracted capsules. At present, the methods for clinical treatment of joint contracture mainly include two major categories:stretching therapy, physical factor therapy, exercise therapy, botulinum toxin injection and other non-surgical treatments, arthroscopic lysis, open lysis, and other surgical treatments. Surgical treatment is performed when non-surgical treatment is difficult to achieve further improvement. It has a good effect on mild to moderate joint contracture, but it is difficult to completely restore joint activity for serious joint contracture. Although clinical treatment methods are diverse, the clinical effects are staggered and the effectiveness of their treatment is controversial. Joint contracture is an important challenge faced by orthopedics and rehabilitation physicians, therapists and patients. The review summarized the pathogenesisand treatment of joint contracture and provided a theoretical basis for clinical diagnosis and treatment.
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Atividades Cotidianas , Contratura , Fibroblastos , Fibrose , Humanos , Cápsula Articular , Fator de Crescimento Transformador beta1RESUMO
Programmed cell death 4 (PDCD4) is a newly identified tumor suppressor that can inhibit activator protein (AP)-1 activation and protein translation. Our previous studies indicate that lost or reduced PDCD4 expression is associated with the progression of ovarian carcinoma. However, direct evidence that PDCD4 inhibits malignant phenotype of human cancer cells is limited. In the present study, we found that PDCD4 expression in ovarian cancer cell lines (SKOV3, 3AO, and CAOV3) inhibited significantly their proliferation and cell cycle progression, and induced apoptosis. More importantly, up-regulation of PDCD4 expression decreased the colony-forming capacity of ovarian cancer cells in vitro and tumorigenic capacity in mice. These results demonstrate that PDCD4 can suppress the malignant phenotype of ovarian cancer cells, and may represent a novel therapeutic target for the treatment of ovarian cancer.
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Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma/patologia , Neoplasias Ovarianas/patologia , Proteínas de Ligação a RNA/metabolismo , Animais , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/fisiologia , Carcinoma/genética , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Nus , Neoplasias Ovarianas/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/fisiologia , Distribuição Aleatória , Fator de Transcrição AP-1/antagonistas & inibidores , Transfecção , Carga Tumoral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
AIM: To study the effect of an innovative micro-dissection procedure by radiofrequency ablation (MRA) in removing eyelid nevus. METHODS: Fifty-six consecutive outpatients with eyelid nevus were treated with MRA using a monopolar device. The effect of MRA was determined after following-up for 6mo to 5y. RESULTS: Fifty-two cases (52 eyes, 92.9%) were cured once, and 4 cases (4 eyes, 7.1%) received second treatment for small residual. All cases healed well after surgery, with no pigmentation, no scars, no loss of eyelashes, no deformation of eyelid margin. There was no visual impairment after healing. CONCLUSION: MRA of eyelid nevus using the XL-RFA device is highly efficient without significant complications.
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Programmed cell death 4 (Pdcd4) was found to be related to apoptosis upon first discovery. It was later found to play the role of tumor suppressor gene in a variety of tumors by inhibiting transcription and translation. Recently, it has been proposed that it may play an important role in some inflammatory diseases and in the immune response. In our previous study, deficiency of Pdcd4 was found to attenuate the formation of atherosclerotic plaques. This might be because deficiency of Pdcd4 may increase IL-10 expression and lipoautophagy by macrophages and attenuate the formation of foam cells. However, the effect of Pdcd4 on the subsets of T cells in hyperlipidemic mice still remained unclear. In the present study, results showed that Pdcd4 deficiency decreased the percentage of CD8+ T cells and increased that of regulatory T cells (Tregs) under hyperlipidemic conditions both in vitro and in vivo, which may be due to the reduced expression of co-stimulatory molecules CD28 and CD137, and the enhancive expression of co-inhibitory molecules CTLA-4. These results indicated that endogenous Pdcd4 promotes immune response mediated by T cells through regulation of the co-stimulatory molecules expression, which may contribute to the development of advanced atherosclerotic plaques. The current work provides new data to understand the role of Pdcd4 in different T cell subsets under hyperlipidemic microenvironment.
Assuntos
Proteínas Reguladoras de Apoptose/deficiência , Proteínas Reguladoras de Apoptose/metabolismo , Hiperlipidemias/metabolismo , Proteínas de Ligação a RNA/metabolismo , Subpopulações de Linfócitos T/metabolismo , Animais , Apoptose/fisiologia , Antígenos CD28/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Células Espumosas/metabolismo , Interleucina-10/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Placa Aterosclerótica/metabolismo , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismoRESUMO
OBJECTIVE: To identify the role of serum cytokine levels prior allogeneic hematopoietic stem cell trans-plantation (allo-HSCT) in the outcome of severe aplastic anemia (SAA) patients received allo-HSCT treatment. METHODS: The clinical data of 117 SAA patients received allo-HSCT were enrolled in this study. The overall survival (OS), graft versus host disease (GVHD) incidence and relationship of serum cytokines with OS and major transplantation complications were retrospectively analyzed. RESULTS: The patients enrolled in this study included 78(66.7%) cases received HSCT matched sibling donors (MSD), 12(10.2%) HSCT of unrelated donors (MUD) and 27 cases received HSCT of haploidentical donors (HID). The 5-years OS was 76.0%(95% CI: 64.4-87.5%); aGVHD cumulative incidence was 49.6%(95% CI: 40.4%-58.8%) and cumulative incidence cGVHD was 31.6%(95% CI:23.1%-40.2%). MSD allo-HSCT had a significantly higher 5-years OS as compared with the other donors(82.3%±6.6% vs 61.3%±11.7%, P<0.05). HLA matching, donor's age, cytomegalovirus/ Epstein-Barr virus (CMV/EBV) infection were important factors of affecting occurence of aGVHD. The patients with higher serum IL-6 had reduced platelet recovery time after transplantation (14.6±1.8 vs 18.3±2.6 d)(P=0.050) and higher serum TNF-α level accompanied by a lower incidence of CMV/EBV infection (37.8%±11.1% vs 58.8±16.8%)(P<0.05). CONCLUSION: MSD allo-HSCT is the effective treatment for SAA patients. Donor's type remains the strong predictor of survival. The serum levels IL-6 and TNF-α before transplantation associate with platelet recovery and CMV/EBV infection.
Assuntos
Anemia Aplástica , Citocinas , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Clinical xenotransplantations have been hampered by human preformed antibody-mediated damage of the xenografts. To overcome biological incompatibility between pigs and humans, one strategy is to remove the major antigens [Gal, Neu5Gc, and Sd(a)] present on pig cells and tissues. Triple gene (GGTA1, CMAH, and ß 4GalNT2) knockout (TKO) pigs were produced in our laboratory by CRISPR-Cas9 targeting. To investigate the antigenicity reduction in the TKO pigs, the expression levels of these three xenoantigens in the cornea, heart, liver, spleen, lung, kidney, and pancreas tissues were examined. The level of human IgG/IgM binding to those tissues was also investigated, with wildtype pig tissues as control. The results showed that αGal, Neu5Gc, and Sd(a) were markedly positive in all the examined tissues in wildtype pigs but barely detected in TKO pigs. Compared to wildtype pigs, the liver, spleen, and pancreas of TKO pigs showed comparable levels of human IgG and IgM binding, whereas corneas, heart, lung, and kidney of TKO pigs exhibited significantly reduced human IgG and IgM binding. These results indicate that the antigenicity of TKO pig is significantly reduced and the remaining xenoantigens on porcine tissues can be eliminated via a gene targeting approach.
RESUMO
OBJECTIVE: To study the relationship between the change of regulatory T cell number in CD4+ T subset and the growth of tumor in H22 hepatocellular carcinoma-bearing mice. METHODS: Tumor-bearing mice were established by subcutaneous inoculation of H22 hepatocelluler carcinoma cells. Flow cytometry was used to detect the expression of CD4 and CD25 molecules of the T cells which came from the tumor-bearing mice. The Foxp3 gene expression was detected by RT-PCR and flow cytometry. CD4+ CD25+ T cells and CD4+ CD25- T cells were separated and purified by immuno-magnetic beads. The proliferation and suppressive function of the CD4+ CD25+ T cells coming from tumor-bearing mice was measured by [3H]-thymidines incorporation experiment in vitro, and then effect of CD4+ CD25+ T cells originated from hepatocellular carcinoma-bearing mice on tumor growth was observed in vivo. RESULTS: (1) Compared with mice of the control group, the percentage of CD4+ CD25+ T cells of CD4+ T cells in tumor-bearing mice is not only higher in draining lymph nodes (18.80% < or = 0.06%) vs. (9.50% +/- 0.03%), (P < 0.01), but also higher in non-draining lymph nodes (LN) and spleen (SP), LN: (16.28% +/- 0.02%) vs. (9.50% +/- 0.03%), P < 0.01; SP: (17.28% +/- 0.06%) vs. (11.08% +/- 0.04%), (P < 0.05). The expression of regulatory T cell specific marker Foxp3 gene was also increased. In the same tumor-bearing mice, the number of CD4+ CD25+ T cells in draining lymph node was relatively higher than the contralateral nondraining lymph node, but the difference was statistically not significant (18.8% +/- 0.06%) vs. (16.28% +/- 0.02%), (P > 0.05). (2) The CD4+ CD25+ T cells purified from tumor-bearing mice--like naturally occurring regulatory T cells--were anergic to anti-CD3 monoclonal antibody stimulation in vitro, but it could suppress CD4+ CD25- T cells proliferation. (3) The percentage of CD4+ CD25+ T cells was positively related to tumor size. It could also suppress the anti-tumor effect of CD4+ CD25- T cells in vivo. Conclusion The growth of hepatocellular carcinoma in mice can boost the amount of regulatory T cells. The amount of regulatory T cells is positively related to tumor size, indicating that attack on regulatory T cells could be used as one of modalities in cancer treatment in the future.