[Oblique Lumbar Interbody Fusion Combined With 4-Screw Fixation for Treating Two-Level Degenerative Lumbar Diseases:A Finite Element Study].

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.

Angiotensin II Type 2 Receptor Modulates Synovial Macrophage Polarization by Inhibiting GRK2 Membrane Translocation in a Rat Model of Collagen-Induced Arthritis.

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.

CP-25 alleviates antigen-induced experimental Sjögren's syndrome in mice by inhibiting JAK1-STAT1/2-CXCL13 signaling and interfering with B-cell migration.

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.

Identification of key gene modules and pathways of human glioma through coexpression network.

Glioma causes great harm to people worldwide. Systemic coexpression analysis of this disease could be beneficial for the identification and development of new prognostic and predictive markers in the clinical management of glioma. In this study, we extracted data sets from the Gene Expression Omnibus data set by using "glioma" as the keyword. Then, a coexpression module was constructed with the help of Weighted Gene Coexpression Network Analysis software. Besides, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the genes in these modules. As a result, the critical modules and target genes were identified. Eight coexpression modules were constructed using the 4,000 genes with a high expression value of the total 141 glioma samples. The result of the analysis of the interaction among these modules showed that there was a high scale independence degree among them. The GO and KEGG enrichment analyses showed that there was a significant difference in the enriched terms and degree among these eight modules, and module 5 was identified as the most important module. Besides, the pathways it was enriched in, hsa04510: Focal adhesion and hsa04610: Complement and coagulation cascades, were determined as the most important pathways. In summary, module 5 and the pathways it was enriched in, hsa04510: Focal adhesion and has 04610: Complement and coagulation cascades, have the potential to serve as biomarkers for patients with glioma.

Natural attenuation mechanism and health risk assessment of 1,1,2-trichloroethane in contaminated groundwater.

1,1,2-trichloroethane (TCA) is a contaminant in many pesticide and chemical fields. This study mainly described the potential effectiveness of the natural attenuation of 1,1,2-TCA in groundwater in a typical pesticide-contaminated field in east China. In this study, six typical 1,1,2-TCA-contaminated sites (MW14, MW21, MW25, MW31, MW36 and MW41) were selected, and the field investigation results indicated that there was an obvious decline in the concentrations of 1,1,2-TCA over time in all selected sites. Furthermore, the attenuation rate of 1,1,2-TCA concentration in sites MW14, MW21, MW25, MW31 and MW41 followed the first-order kinetic equation, and the first-order attenuation rate constants were calculated. The health risks of 1,1,2-TCA and its degradation product dichloroethane (DCA) were assessed and compared in site MW14. The result showed that the health risks of 1,1,2-TCA were much higher than those of DCA, and 1,1,2-TCA was the contamination source in this site. 16S rRNA sequencing was also conducted to investigate the diversity of the bacterial community in 1,1,2-trichloroethane (TCA)-contaminated groundwater, and Geobacter, Thauera, Pseudomonas, Diaphorobacter were the main species in the bacterial community.

Optical bistability induced by spin-orbit coupling in the carbon-nanotube quantum dots.

We theoretically investigate steady-state behaviors of carbon nanotube quantum dots with spin-orbit coupling in a unidirectional ring cavity. Our results show that the spin-orbit coupling can induce optical bistability. In addition to the existence of spin-orbit coupling, switching optical bistability to optical multistability or vice versa is realized by adjusting detuning of the probe field. Our results show that the carbon nanotube quantum dots will possibly be a promising candidate for realizing all-optical switching.

A Simple Fluorescence Quenching Method for the Determination of Vanillin Using TGA-capped CdTe/ZnS Nanoparticles as Probes.

Based on the quenching of the fluorescence intensity of thioglycolic acid (TGA)-capped core-shell CdTe/ZnS nanoparticles (NPs) by vanillin, a novel, simple and rapid method for the determination of vanillin was proposed. In aqueous medium, the functionalized core-shell CdTe/ZnS NPs were successfully synthesized with TGA as the capping ligand. TGA-capped core-shell CdTe/ZnS NPs were characterized by using X-ray diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy. Factors affecting the vanillin detection were investigated, and the optimum conditions were also determined. Under the optimum conditions, the relative fluorescence intensity of CdTe/ZnS NPs was linearly proportional to vanillin over a concentration range from 9.4 × 10(-7) to 5.2 × 10(-4) M with a correlation coefficient of 0.998 and a detection limit of 2.6 × 10(-7) M. The proposed method was also employed to detect trace vanillin in cookies with satisfactory results.

A novel route to prepare LaNiO3 perovskite-type oxide nanofibers by electrospinning for glucose and hydrogen peroxide sensing.

Perovskite-type oxide LaNiO(3) nanofibers (LNFs) have been successfully synthesized by electrospinning and sequential calcinations. The electrospun LNFs modified carbon paste electrode was used to construct a nonenzymatic hydrogen peroxide (H(2)O(2)) sensor and glucose biosensor for the first time. The LNFs composition was verified by X-ray diffraction, and the morphologies were examined by scanning electron microscopy and transmission electron microscopy. Cyclic voltammetry and amperometry were used to evaluate the catalytic activity of the LNFs modified electrode towards H(2)O(2) and glucose. By using LNFs as electrocatalysts, the modified electrode showed high electrocatalytic activity for the oxidation of H(2)O(2) and glucose. Under the optimized conditions, the H(2)O(2) sensor exhibited a low detection limit down to 33.9 nM with a wide linear range from 0.05 to 1000 µM. The nonenzymatic sensor also showed fast response, long-term stability as well as a low detection limit for glucose.

Analysis of stress and stabilization in adolescent with osteoporotic idiopathic scoliosis: finite element method.

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.

Biomechanical evaluation of two-level oblique lumbar interbody fusion combined with posterior four-screw fixation：A finite element analysis.

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.

Effect of Displacement Degree of Distal Chevron Osteotomy on Metatarsal Stress: A Finite Element Method.

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.

New Insights for the Design of Bionic Robots: Adaptive Motion Adjustment Strategies During Feline Landings.

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.

Biomechanical characteristics of 2 different posterior fixation methods of bilateral pedicle screws: A finite element analysis.

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.

The Effect of Concave-Side Intertransverse Ligament Laxity on the Stress of AIS Lumbar Spine Based on Finite Element Method.

(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.

A new method proposed to explore the feline's paw bones of contributing most to landing pattern recognition when landed under different constraints.

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.

HepaCAM induces G1 phase arrest and promotes c-Myc degradation in human renal cell carcinoma.

Hepatocyte cell adhesion molecule (hepaCAM) encodes a generally inactive phosphorylated glycoprotein which mediates cancer cell proliferation, migration, and differentiation. We have reported that hepaCAM is down-regulated in renal cell carcinoma (RCC) and takes responsibility of cell growth inhibition. However, the precise mechanisms of hepaCAM inhibits cell growth is still unknown. In this study, we demonstrated that re-expression of hepaCAM can cause an accumulation in G0/G1 phase in 786-0 cells. This reaction was accompanied by a substantial reduction of c-Myc expression through using an ectopic hepaCAM expression system. Furthermore, we found a comparable decrease in proliferation and G0/G1 accumulation of 786-0 and RC-2 cells after treatment with a small molecule c-Myc inhibitor, 10058-F4. This indicated that the down regulation of c-Myc was an essential process in controlling growth inhibitory actions of hepaCAM. Nevertheless, re-expression of hepaCAM results in apparent reduction of c-Myc protein with no corresponding reduction of c-Myc mRNA. This suggests that this reaction might take place at a post-transcriptional level rather than transcriptional one. Consistent with these findings, hepaCAM decreased c-Myc stability by increasing the proportion of c-Myc phosphorylation on T58 which can be abrogated by a proteasomal inhibitor (MG132). Thus, our research implies that the decrease in c-Myc protein expression, resulting from ectopic expression of hepaCAM, may contribute to the inhibition of proliferation in these cells.

Finite element analysis of the lumbar spine in adolescent idiopathic scoliosis subjected to different loads.

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.

Deficiency of ß-arrestin2 alleviates apoptosis through GRP78-ATF6-CHOP signaling pathway in primary Sjögren's syndrome.

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.

Nomogram for Predicting Bone Development State of Female Children and Adolescents-A Fast Screening Approach Based on Pubes Stages for Growth and Development.

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.

Alleviating effect of paeoniflorin-6'-O-benzene sulfonate in antigen-induced experimental Sjögren's syndrome by modulating B lymphocyte migration via CXCR5-GRK2-ERK/p38 signaling pathway.

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.