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1.
Int J Gen Med ; 17: 3907-3918, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39257611

RESUMO

Objective: Hepatitis B virus (HBV) infection is a significant global public health concern, with variable prevalence rates across regions. The prevalence of transfusion-transmitted HBV infection (TT-HBV) via donated blood necessitates an evaluation of blood safety and potential risks to the population. This study assessed the prevalence of HBV infection among blood donors in Southwestern China over 6 years. Methods: We analyzed 903,023 blood donations from a central blood center in Southwestern China between January 2017 and December 2022. The prevalence of HBV in donations was determined for one-time and repeat donors, considering birth cohorts and covariates. Demographic characteristics, donation frequency, and anti-HBV antibody status were analyzed to estimate the incidence of TT-HBV. Results: One-time donors provided 47.78% of the samples, and 52.22% were from repeat donors. The HBV prevalence decreased from 1.0% in 2017 to 0.87% in 2022 in one-time donors and from 0.30% to 0.09%, respectively, in repeat donors. A significantly lower HBV prevalence was identified in the post-1992 birth cohort (0.33%) than in the pre-1992 birth cohort (1.67%). The estimated incidences of TT-HBV occurring from one-time donors, repeat donors, post-1992 birth cohort donors, and pre-1992 birth cohort donors were 20.76, 13.84, 0.82, and 20.98 per 104 person-years, respectively. Conclusion: Our findings indicate a decreasing trend in HBV prevalence among blood donors in Southwestern China over the 6-year study period. This decline may be attributed to the widespread administration of HBV vaccinations and stringent screening measures implemented by blood donation centers. Continuous monitoring for HBV among blood donors is necessary to evaluate the effectiveness of preventive measures and inform future strategies to reduce transmission.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39282741

RESUMO

The surge in popularity of running has led to a multitude of designs in running shoe technology, notably, there is an increasing trend in toe spring elevation. However, the impact of this design on foot structures during running remains an essential exploration. To investigate the effects of toe spring on the foot during forefoot running, we employed finite element simulation to create two sole models with different toe spring heights (6.5 cm and 8 cm) and ground contact angles (5°, 10°, and 15°). We established and validated two foot-shoe coupling models and compared stress variations in metatarsal bones and the big toe under identical loading and environmental conditions. Higher toe spring resulted in lower peak stress and reduced stress concentration in metatarsal bones. The fourth and fifth metatarsals exhibited increasing stress trends with ground contact angle, with the fifth metatarsal experiencing the most significant stress concentration. In the case of low toe spring, stress on the fifth metatarsal increased from 15.917 MPa (5°) to 27.791 MPa (15°), indicating a rise of 11.874 MPa. Conversely, the first metatarsal showed lower stress, indicating relative safety but reduced functional significance. Moreover, higher toe spring running shoes exerted less pressure on the big toe, with an increasing trend in stress on the big toe with an increase in ground contact angle. Shoes with a higher toe spring design result in reduced pressure on the big toe. Therefore, it is advisable to avoid landing angles greater than 15° to prevent stress fractures resulting from repetitive loading.

3.
Bioengineering (Basel) ; 11(8)2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39199783

RESUMO

BACKGROUND: Physiological curvature changes of the lumbar spine and disc herniation can cause abnormal biomechanical responses of the lumbar spine. Finite element (FE) studies on special weightlifter models are limited, yet understanding stress in damaged lumbar spines is crucial for preventing and rehabilitating lumbar diseases. This study analyzes the biomechanical responses of a weightlifter with lumbar straightening and L4-L5 disc herniation during symmetric bending and lifting to optimize training and rehabilitation. METHODS: Based on the weightlifter's computed tomography (CT) data, an FE lumbar spine model (L1-L5) was established. The model included normal intervertebral discs (IVDs), vertebral endplates, ligaments, and a degenerated L4-L5 disc. The bending angle was set to 45°, and weights of 15 kg, 20 kg, and 25 kg were used. The flexion moment for lifting these weights was theoretically calculated. The model was tilted at 45° in Abaqus 2021 (Dassault Systèmes Simulia Corp., Johnston, RI, USA), with L5 constrained in all six degrees of freedom. A vertical load equivalent to the weightlifter's body mass and the calculated flexion moments were applied to L1 to simulate the weightlifter's bending and lifting behavior. Biomechanical responses within the lumbar spine were then analyzed. RESULTS: The displacement and range of motion (ROM) of the lumbar spine were similar under all three loading conditions. The flexion degree increased with the load, while extension remained unchanged. Right-side movement and bending showed minimal change, with slightly more right rotation. Stress distribution trends were similar across loads, primarily concentrated in the vertebral body, increasing with load. Maximum stress occurred at the anterior inferior margin of L5, with significant stress at the posterior joints, ligaments, and spinous processes. The posterior L5 and margins of L1 and L5 experienced high stress. The degenerated L4-L5 IVD showed stress concentration on its edges, with significant stress also on L3-L4 IVD. Stress distribution in the lumbar spine was uneven. CONCLUSIONS: Our findings highlight the impact on spinal biomechanics and suggest reducing anisotropic loading and being cautious of loaded flexion positions affecting posterior joints, IVDs, and vertebrae. This study offers valuable insights for the rehabilitation and treatment of similar patients.

4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 341-347, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38953258

RESUMO

Objective To demonstrate the feasibility of oblique lumbar interbody fusion (OLIF) combined with 4-screw fixation for treating two-level lumbar degenerative diseases.Methods An intact finite element model of L3-S1 (M0) was constructed and validated.Then,we constructed the M1 model by simulating OLIF surgery at L3/4 and L4/5 segments on the M0 model.By attachment of posterior 4-screw or 6-screw fixation to the M1 model,three 4-screw fixation models (M2-M4) and one 6-screw fixation model (M5) were established.The segmental and overall range of motion (ROM) and the peak von Mises stresses of superior endplate,cage,and posterior screw-rod were investigated under each implanted condition.Results Under the motion modes of forward flexion,backward extension,bilateral (left and right) flexion,and left and right rotation,the L3/4 ROM of M2 model and L4/5 ROM of M3 model increased,while the L3/4 and L4/5 ROM of M4 and M5 models significantly decreased compared with those of M1 model.Under all motion modes,the L4 superior endplate in M2 model and the L5 superior endplate in M3 model showed the maximum peak von Mises stress,and the peak von Mises stresses of L4 and L5 superior endplates in M4 and M5 models were close.The L3/4 cage in M2 model and the L4/5 cage in M3 model showcased the largest peak von Mises stress,and the peak von Mises stresses of cages in M4 and M5 models were close.The peak stresses of internal fixation in M2-M5 models were close.Conclusion Four-screw fixation can replace 6-screw fixation in the OLIF surgery for treating two-level degenerative lumbar diseases.


Assuntos
Parafusos Ósseos , Análise de Elementos Finitos , Vértebras Lombares , Fusão Vertebral , Fusão Vertebral/métodos , Fusão Vertebral/instrumentação , Humanos , Vértebras Lombares/cirurgia
5.
Sensors (Basel) ; 24(14)2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39066155

RESUMO

(1) This study examined the impact of fatigue and unanticipated factors on knee biomechanics during sidestep cutting and lateral shuffling in female basketball players, assessing the potential for non-contact anterior cruciate ligament (ACL) injuries. (2) Twenty-four female basketball players underwent fatigue induction and unanticipated change of direction tests, and kinematic and kinetic parameters were collected before and after fatigue with a Vicon motion capture system and Kistler ground reaction force (GRF) sensor. (3) Analysis using two-way repeated-measures ANOVA showed no significant interaction between fatigue and unanticipated factors on joint kinematics and kinetics. Unanticipated conditions significantly increased the knee joint flexion and extension angle (p < 0.01), decreased the knee flexion moment under anticipated conditions, and increased the knee valgus moment after fatigue (p ≤ 0.05). One-dimensional statistical parametric mapping (SPM1d) results indicated significant differences in GRF during sidestep cutting and knee inversion and rotation moments during lateral shuffling post-fatigue. (4) Unanticipated factors had a greater impact on knee load patterns, raising ACL injury risk. Fatigue and unanticipated factors were independent risk factors and should be considered separately in training programs to prevent lower limb injuries.


Assuntos
Basquetebol , Articulação do Joelho , Humanos , Basquetebol/fisiologia , Feminino , Fenômenos Biomecânicos/fisiologia , Articulação do Joelho/fisiologia , Adulto Jovem , Lesões do Ligamento Cruzado Anterior/fisiopatologia , Adulto , Fadiga/fisiopatologia , Amplitude de Movimento Articular/fisiologia
6.
Front Bioeng Biotechnol ; 12: 1435554, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39070160

RESUMO

Flatfoot is characterized by the collapse of the medial longitudinal arch, eversion of the rearfoot and abduction of the loaded forefoot. Orthopedic insoles are the frequently recommended treatment to support the arch of the foot, adjust the structure of the foot, reduce pain, improve stability and new techniques have been applied to the design of orthopedic insoles in recent years. However, the effectiveness of orthopedic insoles in different motions is still debated from the perspective of biomechanics. Therefore, this study aimed to explore the impact of orthopedic insoles on the kinematics and kinetics of lower limb motion, and to verify effectiveness and propose possible future research directions. We conducted a literature search across three databases employing Boolean operations and filtered results based on eligibility criteria. A total of 671 relevant literature were searched in this review, and 19 literature meeting the requirements were finally included. The results showed that: 1) orthopedic insoles were effective when patients walk, run and jump from the perspective of biomechanics; 2) orthopedic insoles had different result on the change of ankle sagittal angle, moment and peak pressure in the metatarsal region; 3) Whether the effect of insoles, which uses new techniques such as different 3D printed technologies and adds various accessories, can be further improved remains to be further studied; 4) Follow-up studies can pay more attention to the differences between diverse populations, increase the breadth of running and jumping and other movements research and long-term intervention.

7.
Front Bioeng Biotechnol ; 12: 1387768, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39040495

RESUMO

Background: The plantar vault, comprising the transverse and longitudinal arches of the human foot, is essential for impact absorption, elastic energy storage, and propulsion. Recent research underscores the importance of the transverse arch, contributing over 40% to midfoot stiffness. This study aimed to quantify biomechanical responses in the ankle-foot complex by varying the stiffness of the deep metatarsal transverse ligament (DTML). Methods: Using CT image reconstruction, we constructed a complex three-dimensional finite element model of the foot and ankle joint complex, accounting for geometric complexity and nonlinear characteristics. The focus of our study was to evaluate the effect of different forefoot transverse arch stiffness, that is, different Young's modulus values of DTML (from 135 MPa to 405 MPa), on different biomechanical aspects of the foot and ankle complex. Notably, we analyzed their effects on plantar pressure distribution, metatarsal stress patterns, navicular subsidence, and plantar fascial strain. Results: Increasing the stiffness of the DTML has significant effects on foot biomechanics. Specifically, higher DTML stiffness leads to elevate von Mises stress in the 1st, 2nd, and 3rd metatarsals, while concurrently reducing plantar pressure by 14.2% when the Young's modulus is doubled. This stiffening also impedes navicular bone subsidence and foot lengthening. Notably, a 100% increase in the Young's modulus of DTML results in a 54.1% decrease in scaphoid subsidence and a 2.5% decrease in foot lengthening, which collectively contribute to a 33.1% enhancement in foot longitudinal stiffness. Additionally, doubling the Young's modulus of DTML can reduce the strain stretch of the plantar fascia by 38.5%. Conclusion: Preserving DTML integrity sustains the transverse arch, enhancing foot longitudinal stiffness and elastic responsiveness. These findings have implications for treating arch dysfunction and provide insights for shoe developers seeking to enhance propulsion.

8.
Clin Neurol Neurosurg ; 225: 107597, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36696847

RESUMO

OBJECTIVE: By constructing the three-dimensional finite element model of two-level OLIF lumbar spine, the aim of this study was to demonstrate the feasibility and effectiveness of posterior four-screw fixation for treatment of two-level lumbar degenerative diseases from the perspective of biomechanics. METHODS: An intact L3-S1 segment nonlinear lumbar finite element model (M0) was constructed from the CT scanning data of a healthy adult. After verification, two-level OLIF procedure were simulated, and three patterns of finite element analysis models were constructed: two-level stand-alone OLIF group (M1), two-level OLIF + four-screw fixation group (M2) and two-level OLIF + six-screw fixation group (M3). Range of motion, stress of the cage, and stress of fixation were evaluated in the different models. RESULTS: Under various motion modes,the ROM of M2 and M3 were significantly lower than those of M1. The ROM reduction of M2 relative to M1 was much greater than that of M3 relative to M2. Moreover, the peak von Mises stresses of endplates in M2 were almost the same as those in M3. In terms of the maximum stresses of cages, M2 and M3 were essentially identical. Besides, the maximum stresses of posterior instrumentation in M2 and M3 were similar, which were mainly concentrated at the root of pedicle screws. CONCLUSION: There were no significant differences between M2 and M3 from the biomechanical analysis. In two-level OLIF, posterior four-screw fixation can replace six-screw fixation, which reduces surgical trauma and decreases economic burden of patients, and will be a cost-effective alternative.


Assuntos
Parafusos Pediculares , Fusão Vertebral , Adulto , Humanos , Análise de Elementos Finitos , Fusão Vertebral/métodos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Fenômenos Biomecânicos , Amplitude de Movimento Articular
9.
Comput Methods Biomech Biomed Engin ; 26(1): 12-24, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35393912

RESUMO

Objective: To explore the effect of osteoporosis on the stress, stability, and lumbar intervertebral disc of AIS lumbar vertebrae by finite element method. Better understand the biomechanical characteristics of osteoporotic scoliosis.Methods: Based on the CT images of normal lumbar vertebrae and lumbar vertebrae with AIS, the finite element models were established to simulate the estimated osteoporosis by changing the Young's modulus of cortical bone, cancellous bone, and endplate. Four finite element models of normal lumbar, osteoporotic lumbar, normal AIS lumbar and osteoporotic AIS lumbar were established, and the same load and boundary conditions were applied respectively. The displacement, stress, and intervertebral disc strain of the four models were compared to explore the effect of osteoporosis on the stability and injury risk of AIS.Results: After suffering from osteoporosis, under the same load, the displacement of lumbar spine increases, the stability decreases, and the stability of AIS lumbar spine decrease more obviously, especially under extension load. Suffering from osteoporosis will increase the stress of lumbar spine, AIS lumbar spine increases more obviously, and the stress is more concentrated, Osteoporotic lumbar spine only affects the strain of intervertebral disc when AIS lumbar spine bends on the concave side, resulting in greater strain behind the concave side of intervertebral disc.Conclusions: AIS patients with OP have lower lumbar stability, a higher risk of fracture of lumbar vertebrae, and spinal nerves are more likely to be compressed by intervertebral discs. OP can aggravate the scoliosis of lumbar vertebrae.


Assuntos
Disco Intervertebral , Osteoporose , Escoliose , Humanos , Adolescente , Escoliose/diagnóstico por imagem , Análise de Elementos Finitos , Vértebras Lombares/diagnóstico por imagem , Osteoporose/diagnóstico por imagem , Fenômenos Biomecânicos
10.
Bioengineering (Basel) ; 9(12)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36550930

RESUMO

(1) Background: Scoliosis has the mechanical characteristic of asymmetric stress distribution, which is one of the reasons for the aggravation of scoliosis. Bracing therapy is the best treatment for AIS, but it is difficult and costly to operate. Is it possible to reduce pressure in the concave side by relaxing the ITL in the concave side of scoliosis, so as to improve the abnormal stress distribution of scoliosis? In this paper, a finite element method was used to simulate the effect of the relaxation of concave-side ITL on the stress of a lumbar spine with scoliosis, which provides some guidance for the treatment of scoliosis. (2) Methods: Using CT images of a patient with scoliosis whose Cobb Angle was 43° and Lordosis Angle was 45, a scoliosis lumbar was established, and Young's modulus of the ITL of the concave-side lumbar spine was reduced by 95% to simulate ligament relaxation. By comparing the stress condition of the model vertebral body with no ligament relaxation, the effect of concave-side ITL relaxation on the mechanical characteristics of scoliosis lumbar spine was explored. (3) Results: An effective and complete model of the lumbar spine was established. The concave ITL relaxed, which only had a great impact on the bending loads. After the ligament was relaxed, the stability of the spine was reduced. Stress concentration on the concave side of vertebrae and the IVD was aggravated. Under loads on the convex side, the maximum stress on the vertebral body and the IVD increased significantly, making lumbar vertebrae more vulnerable to injury. (4) Conclusions: Laxity of the ITL on the concave side of the AIS lumbar only affects the bending load. Laxity of the concave-side ligament will reduce the stability of the lumbar, aggravate the uneven stress distribution of scoliotic lumbar vertebrae, increase the risk of IVD injury, and be unfavorable for the scoliotic lumbar spine. Relaxation of the concave ITL alone is not an effective way to treat scoliosis.

11.
Front Vet Sci ; 9: 1011357, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36299631

RESUMO

Felines are generally acknowledged to have natural athletic ability, especially in jumping and landing. The adage "felines have nine lives" seems applicable when we consider its ability to land safely from heights. Traditional post-processing of finite element analysis (FEA) is usually based on stress distribution trend and maximum stress values, which is often related to the smoothness and morphological characteristics of the finite element model and cannot be used to comprehensively and deeply explore the mechanical mechanism of the bone. Machine learning methods that focus on feature pattern variable analysis have been gradually applied in the field of biomechanics. Therefore, this study investigated the cat forelimb biomechanical characteristics when landing from different heights using FEA and feature engineering techniques for post-processing of FEA. The results suggested that the stress distribution feature of the second, fourth metacarpal, the second, third proximal phalanx are the features that contribute most to landing pattern recognition when cats landed under different constraints. With increments in landing altitude, the variations in landing pattern differences may be a response of the cat's forelimb by adjusting the musculoskeletal structure to reduce the risk of injury with a more optimal landing strategy. The combination of feature engineering techniques can effectively identify the bone's features that contribute most to pattern recognition under different constraints, which is conducive to the grasp of the optimal feature that can reveal intrinsic properties in the field of biomechanics.

12.
Medicine (Baltimore) ; 101(36): e30419, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086784

RESUMO

BACKGROUND: To explore the biomechanical characteristics of 2 posterior bilateral pedicle screw fixation methods using finite element analysis. METHODS: A normal L3-5 finite element model was established. Based on the verification of its effectiveness, 2 different posterior internal fixation methods were simulated: bilateral pedicle screws (model A) were placed in the L3 and L5 vertebral bodies, and bilateral pedicle screws (model B) were placed in the L3, L4, and L5 vertebral bodies. The stability and stress differences of intervertebral discs, endplates, screws, and rods between models were compared. RESULTS: Compared with the normal model, the maximum stress of the range of motion, intervertebral disc, and endplate of the 2 models decreased significantly. Under the 6 working conditions, the 2 internal fixation methods have similar effects on the stress of the endplate and intervertebral disc, but the maximum stress of the screws and rods of model B is smaller than that of model A. CONCLUSIONS: Based on these results, it was found that bilateral pedicle screw fixation in 2 vertebrae L3 and L5 can achieve similar stability as bilateral pedicle screw fixation in 3 vertebrae L3, L4, and L5. However, the maximum stress of the screw and rod in model B is less than that in model A, so this internal fixation method can effectively reduce the risk of fracture. The 3-dimensional finite element model established in this study is in line with the biomechanical characteristics of the spine and can be used for further studies on spinal column biomechanics. This information can serve as a reference for clinicians for surgical selection.


Assuntos
Parafusos Pediculares , Fusão Vertebral , Fenômenos Biomecânicos , Análise de Elementos Finitos , Humanos , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos
13.
Front Vet Sci ; 9: 836043, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35529841

RESUMO

Felines have significant advantages in terms of sports energy efficiency and flexibility compared with other animals, especially in terms of jumping and landing. The biomechanical characteristics of a feline (cat) landing from different heights can provide new insights into bionic robot design based on research results and the needs of bionic engineering. The purpose of this work was to investigate the adaptive motion adjustment strategy of the cat landing using a machine learning algorithm and finite element analysis (FEA). In a bionic robot, there are considerations in the design of the mechanical legs. (1) The coordination mechanism of each joint should be adjusted intelligently according to the force at the bottom of each mechanical leg. Specifically, with the increase in force at the bottom of the mechanical leg, the main joint bearing the impact load gradually shifts from the distal joint to the proximal joint; (2) the hardness of the materials located around the center of each joint of the bionic mechanical leg should be strengthened to increase service life; (3) the center of gravity of the robot should be lowered and the robot posture should be kept forward as far as possible to reduce machine wear and improve robot operational accuracy.

14.
Biology (Basel) ; 11(1)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35053125

RESUMO

BACKGROUND: The stress of foot bone can effectively evaluate the functional damage caused by foot deformity and the results of operation. In this study, the finite element method was used to investigate the degree of displacement of distal chevron osteotomy on metatarsal stress and metatarsophalangeal joint load; Methods: Four finite element models of displacement were established by using the CT images of a patient with moderate hallux valgus (hallux valgus angle and intermetatarsal angle were 26.74° and 14.09°, respectively), and the validity of the model was verified. Each finite element model consisted of bones and various cartilage structures, ligaments, and plantar fascia, as well as encapsulated soft tissue. Except for soft tissue, the material properties of other parts were isotropic linear elastic material, and the encapsulated soft tissue was set as nonlinear hyperelastic material. The mesh was tetrahedral mesh. Link elements were used in ligament and plantar fascia. A ground reaction force with a half-body weight was applied at the bottom of the floor to simulate the ground reaction when standing. The upper surfaces of the encapsulated soft tissue, distal tibia, and distal fibula were fixed. The stress distribution of metatarsals and the stress of cartilage of the first metatarsophalangeal joint were compared and analyzed; Results: Compared with the hallux valgus without osteotomy, the stress of the first metatarsals and second metatarsals of 2-4 mm decreased, and the stress of the interarticular cartilage of the first metatarsophalangeal joint with 4 mm was reduced. In the case of 6 mm, the stress value between the first metatarsal and the first metatarsophalangeal joint increased, and 4 mm was the most suitable distance; Conclusions: Compared with the hallux valgus without osteotomy, the stress of the first metatarsals and second metatarsals of 2-4 mm decreased, and the stress of the interarticular cartilage of the first metatarsophalangeal joint with 4 mm was reduced. In the case of 6 mm, the stress value between the first metatarsal and the first metatarsophalangeal joint increased, and 4 mm was the most suitable distance. For the degree of displacement of the distal chevron osteotomy, the postoperative stability and the stress distribution of metatarsal bone should be considered. Factors such as hallux valgus angle, intermetatarsal angle, patient's age, body weight, and metatarsal width should be considered comprehensively. The factors affecting osteotomy need to be further explored. The degree of displacement of osteotomy can be evaluated by FE method before the operation, and the most suitable distance can be obtained.

15.
Int Immunopharmacol ; 101(Pt A): 108281, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34710848

RESUMO

The etiology of primary Sjögren's syndrome (pSS) remains unknown, and there is no ideal drug for the specific treatment of pSS. ß-arrestin2 is a key protein that mediates desensitization and internalization of G protein-coupled receptors (GPCRs) and it participates in inflammatory and immune responses that have been found to mediate apoptosis in autoimmune disease. In this study, we established an experimental Sjögren's syndrome (ESS) mouse model to elucidate the molecular mechanisms of ß-arrestin2 in pSS. First, excessive activation of ß-arrestin2 and GRP78-ATF6-CHOP apoptosis signaling were detected in specimens from pSS patients. In vivo, we found that inhibition of GRP78-ATF6-CHOP apoptosis signaling improved ESS symptoms, and the targeted deletion of ß-arrestin2 significantly increased saliva flow, alleviated salivary gland indices, and improved tissue integrity in the ESS model by downregulating GRP78-ATF6-CHOP apoptosis signaling. In vitro, we used IFNα to stimulate human salivary gland epithelial cells (HSGECs), and the results showed that IFNα activated GRP78-ATF6-CHOP apoptosis signaling, decreased cell viability, and induced apoptosis, which were negatively regulated by the ERS inhibitor 4-PBA. In addition, ß-arrestin2 depletion downregulated GRP78-ATF6-CHOP apoptosis signaling to alleviate cell apoptosis, and the effect depended on the interaction between GRP78 and ß-arrestin2. In summary, our results suggest that excessive activation of GRP78-ATF6-CHOP apoptosis signaling is involved in the pathogenesis of pSS and that ß-arrestin2 encourages inflammation-induced epithelial apoptosis through GRP78-ATF6-CHOP apoptosis signaling. This research further clarified the underlying role of ß-arrestin2 and provided an experimental foundation for ß-arrestin2 depletion in the treatment of the human autoimmune disorder pSS.


Assuntos
Glândulas Salivares/patologia , Síndrome de Sjogren/imunologia , beta-Arrestina 2/metabolismo , Fator 6 Ativador da Transcrição/metabolismo , Animais , Apoptose/imunologia , Linhagem Celular , Modelos Animais de Doenças , Chaperona BiP do Retículo Endoplasmático/metabolismo , Células Epiteliais , Feminino , Humanos , Camundongos , Camundongos Knockout , Glândulas Salivares/imunologia , Transdução de Sinais/imunologia , Síndrome de Sjogren/patologia , Fator de Transcrição CHOP/metabolismo , beta-Arrestina 2/genética
16.
Front Pediatr ; 9: 694958, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34458209

RESUMO

Objective: To develop a nomogram for predicting bone development state (BDS) of female children and adolescents in a large scale. Methods: Four hundred forty-seven female students were designated as the training cohort to develop the predictive model, whereas 196 female students were used as the validation cohort to verify the established model. Bone age, height, body mass, body fat percentage, and secondary sexual characteristics were recorded, and BDS was determined with the chronological age and bone age. Multivariate logistic regression was conducted to determine the factors, and nomogram was developed and validated with the training and validation cohorts, respectively. Results: One hundred forty-seven female students were identified as BDS abnormal in the training cohort (32.9%), and 104 were determined in the validation cohort (53.1%). Age, height, weight, and pubes stage were selected for the predictive model. A nomogram was developed and showed a good estimation, with a C-index of 0.78 and a good calibration in the training cohort. Application of the nomogram to the validation cohort showed a similar C-index of 0.75 and a good calibration. Conclusion: A nomogram for predicting bone development was developed, which can provide a relatively good estimation of BDS for female children and adolescents in Chinese metropolis.

17.
Comput Biol Med ; 136: 104745, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34388472

RESUMO

OBJECTIVE: To explore the biomechanical changes of the lumbar spine segment of idiopathic scoliosis under different loads by simulating six kinds of lumbar spine motions based on a three-dimensional finite element (FE) model. Methods According to the plain CT scan data of L1-L5 segment of an AIS patient, a three-dimensional FE model was established to simulate the biomechanics of lumbar scoliosis under different loads. The lumbar model was reconstructed using Mimics20.0, smoothed in Geomagic2013, assembled in Solidworks 2020, with FE analysis performed using Workbench19.0. Results The completed model had a total of 119029 C3D4 solid elements, 223805 nodes, including finely reconstructed tissue structures. In patients with AIS, the range of motion (ROM) is reduced under all loads. Under flexion loads, the vertebral concave stress distribution is greater; under extension lateral bending, and rotation load at the posterior side of the vertebral body, the stress is concentrated in the L3 vertebral arch. The buffering effect of intervertebral disc on the rotational load is the weakest. Different loads of AIS cause corresponding changes in the force and displacement of different positions of the vertebral body or intervertebral discs. Conclusions The change in physiological shape of the lumbar vertebrae limits the ROM of the lumbar vertebrae. The stress showed a trend of local concentration which located in the concave side of the scoliosis. The stress on the lumbar vertebrae comprising the greatest curvature is the most excessive. The stress in the intervertebral disc under the rotating load is greater than that under other kinds of loads, and the intervertebral disc is more likely to be injured because of the rotating load.


Assuntos
Disco Intervertebral , Escoliose , Adolescente , Fenômenos Biomecânicos , Análise de Elementos Finitos , Humanos , Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Amplitude de Movimento Articular , Rotação , Escoliose/diagnóstico por imagem
18.
Lab Invest ; 101(8): 1084-1097, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32620868

RESUMO

The etiology of primary Sjögren's syndrome (pSS) remains unknown, and there is no complete curative drug. In this study, we treated a mouse model of the submandibular gland (SG) protein-immunized experimental Sjögren's syndrome (ESS) with paeoniflorin-6'-O-benzene sulfonate (termed CP-25) to evaluate the potential therapeutic effects of CP-25. Through in vivo experiments, we found that CP-25 increased saliva flow, alleviated the salivary gland indexes, and improved tissue integrity in the ESS model. The viability of splenocytes and B-lymphocyte migration from spleen were reduced in ESS mice. Furthermore, CP-25 decreased the expression of IgG antibodies, anti-SSA and anti-SSB antibodies and modulated the levels of cytokines in the serum of SS mice. The numbers of total B lymphocytes, plasma cells (PCs), and memory B cells diminished in the salivary gland. Increased expression of the JAK1-STAT1-CXCL13 axis and IFNα was found in human tissue isolated from pSS patients. In vitro, after stimulation with IFNα, the levels of CXCL13 mRNA and CXCL13 in human salivary gland epithelial cells (HSGEC) increased, while CP-25 counteracted the secretion of CXCL13 and downregulated the expression of CXCL13. IFN-α activated the JAK1-STAT1/2-CXCL13 signaling pathway in HSGEC, which was negatively regulated by additional CP-25. As a consequence, B-cell migration was downregulated in coculture with IFN-α-stimulated HSGEC. Taken together, this study demonstrated that the therapeutic effects of CP-25 were associated with the inhibition of the JAK1-STAT1/2-CXCL13 signaling pathway in HSGEC, which impedes the migration of B cells into the salivary gland. We identified the underlying mechanisms of the therapeutic effect of CP-25 and provided an experimental foundation for CP-25 as a potential drug in the treatment of the human autoimmune disorder pSS.


Assuntos
Linfócitos B/efeitos dos fármacos , Glucosídeos/farmacologia , Monoterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Síndrome de Sjogren/metabolismo , Animais , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CXCL13/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Janus Quinase 1/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição STAT/metabolismo , Glândula Submandibular/citologia , Glândula Submandibular/metabolismo , Glândula Submandibular/patologia
19.
J Immunol ; 205(11): 3141-3153, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33148713

RESUMO

The chronic inflammatory autoimmune disease rheumatoid arthritis (RA) is characterized by an infiltration of activated proinflammatory immune cells into the joint that is accompanied by an overproduction of various mediators, leading to destruction of cartilage and bone erosion. Angiotensin II type 2 receptor (AT2R) is involved in antioxidative, anti-inflammatory, and antifibrotic responses. Synovial macrophages (SMs) are a type of tissue macrophages that are derived from bone marrow cells. SMs plays a central role in synovial regional immunization, which is significantly increased in both collagen-induced mice with arthritis mice and RA patients. AT2R activation caused a reversal of the polarization of SMs in the joint from the proinflammatory M1 SM to the tolerogenic, benign M2 SM. In consequence, this switch resulted in an attenuated form of the joint pathology in a rat model of collagen-induced arthritis. These results were mechanistically linked to the observation that GRK2 was translocated into cytoplasm, and ERK1/2 and NF-κB activation were inhibited. These findings open the way to a new therapeutic approach using an activation of AT2R to subvert joint inflammation in RA.


Assuntos
Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Colágeno/farmacologia , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Macrófagos/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Membrana Sinovial/metabolismo , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Transporte Proteico/fisiologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia
20.
Int Immunopharmacol ; 80: 106199, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31955068

RESUMO

Primary Sjögren's syndrome (pSS) is an autoimmune disease of unresolved aetiology that affects the exocrine glands. Clinical symptoms frequently also involve skin, liver, kidney and neurovascular components. The pathogenesis of pSS is still unclear but B cell hyperactivity has been identified as a hallmark of pSS. Currently, a curative therapeutic agent is lacking. In this study, we explored whether paeoniflorin-6'-O-benzene (CP-25) exerted therapeutic effects through regulating B lymphocyte migration via CXCR5-GRK2-MAPK mediated signaling pathways in a mouse model of antigen-induced, experimental Sjögren's syndrome (ESS). We found that CP-25 increased the salivary flow and alleviated the histopathology of ESS. Furthermore, CP-25 reduced the viability of B lymphocyte and limited the target organs index. In the peripheral blood and salivary gland of ESS mice, CP-25 down-regulated the proportion of total B cells, CXCR5+ B cells and PDCA1 + CD19- and limited the presence of phosphorylated (p-) p38 and ERK (p-ERK). Besides, CP-25 increased the percentage of memory B cells in the peripheral blood and reduced it in salivary gland. Furthermore, in vitro, CP-25 down-regulated p-p38, p-ERK, CXCR5 and membrane GRK2, and increased cytoplasm GRK2 in Maver-1 cells, a mantle cell lymphoma cell line, causing a lower migration ability of Maver-1 cells. Thus, we define CP-25 as a novel compound that is a potent therapeutic agent for pSS which modulates B lymphocyte subsets and impacts the migration of B lymphocytes through regulating the CXCR5-GRK2-ERK/p38 signaling pathway.


Assuntos
Antirreumáticos/uso terapêutico , Glucosídeos/uso terapêutico , Monoterpenos/uso terapêutico , Síndrome de Sjogren/tratamento farmacológico , Animais , Antígenos , Antirreumáticos/farmacologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/fisiologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/imunologia , Feminino , Quinase 2 de Receptor Acoplado a Proteína G/imunologia , Glucosídeos/farmacologia , Humanos , Camundongos Endogâmicos C57BL , Monoterpenos/farmacologia , Receptores CXCR5/imunologia , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/imunologia , Síndrome de Sjogren/imunologia , Baço/efeitos dos fármacos , Baço/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia
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