BACKGROUND:Troxerutin has been found to have a significant ameliorative effect on brain disorders,but there are fewer studies on the effects of troxerutin on the treatment of cerebral infarction and on neuronal cells. OBJECTIVE:To investigate the mechanism by which troxerutin regulates nuclear factor-κB signaling pathway to reduce brain injury and neuronal apoptosis in cerebral infarction rats. METHODS:Fifty clean grade rats were randomized into healthy group,model group,and troxerutin+nuclear factor-κB agonist group,troxerutin group,and nuclear factor-κB inhibitor group.Except for the healthy group,all other groups were used to establish a rat model of cerebral infarction by arterial ligation.The healthy and model groups were treated once a day with an equal amount of physiological saline by gavage.The troxerutin+nuclear factor-κB agonist group was intervened with 72 mg/kg troxerutin by gavage+20 mg/kg RANK intraperitoneally.The troxerutin group was treated with 72 mg/kg troxerutin by gavage.The nuclear factor κB inhibitor group was intervened intraperitoneally with 120 mg/kg nuclear factor κB inhibitor pyrrolidine disulfiram.Administration in each group was given once a day for 30 continuous days.Zea-longa was used to detect neurological damage in rats,hematoxylin-eosin staining was used to observe pathological changes,TUNEL was used to detect neuronal apoptosis,and immunoblotting and PCR were used to detect the expression of nuclear factor-κB p65 and nuclear factor-κB p50 at protein and mRNA levels,respectively. RESULTS AND CONCLUSION:Compared with the healthy group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65,nuclear factor-κB p50 mRNA and protein expression levels were elevated in the model group(P＜0.05).Compared with the model group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were decreased in the troxerutin+nuclear factor-κB agonist group(P＜0.05).Compared with the troxerutin+nuclear factor-κB agonist group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were reduced in the troxerutin group and nuclear factor-κB inhibitor group(P＜0.05).In addition,there was no difference between the troxerutin group and the nuclear factor-κB inhibitor group(P＞0.05).In the model group,there was a large number of cytoplasmic vacuolation,obvious edema and necrosis,and a large number of inflammatory cell infiltrations.In the troxerutin+nuclear factor-κB agonist,the swelling of brain tissue was reduced,and reticulate structures and condensed cells were reduced,still with some edema.In the troxerutin group and nuclear factor-κB inhibitor group,brain tissue swelling,neuronal edema degeneration,cytoplasmic vacuolation and neuronal nucleus consolidation were reduced,and the inflammatory cell infiltration was significantly decreased.To conclude,troxrutin can reduce the expression of neurological impairment,inhibit neuronal apoptosis and improve the pathological injury of brain tissue in rats with cerebral infarction,and its mechanism of action may be related to the modulation of nuclear factor-κB expression and related signaling pathways.

Objective:To investigate the response of mandibular condylar chondroprogenitors to flow fluid shear stress(FFSS).Methods:Chondroprogenitors were in vitro cultured and stimulated with FFSS that can cause cell degeneration,and treated with sec-ond-generation high-throughput RNA sequencing.Differential gene expression was screened using DESeq2 software for gene ontology(GO)functional enrichment analysis,kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis and protein-protein interaction(PPI)network analysis.qRT-PCR was performed to validate the core genes screened by PPI.Results:A total of 1996 differentially expressed genes were obtained,mainly including inflammatory response and cell cycle related molecules.Among them,Actal,Atf3,Ccl2,116,Nfkbia,Ret and Vcaml were identified as the core genes.Conclusion:FFSS stimulation affects chondroprogenitor function by acting on inflammatory responses and cell cycle-related signaling pathways in chondroprogenitors.

T cell immunoglobulin and ITIM domain (TIGIT) is a novel immune checkpoint that has been considered as a target in cancer immunotherapy. Current available bioassays for measuring the biological activity of therapeutic antibodies targeting TIGIT are restricted to mechanistic investigations because donor primary T cells are highly variable. Here, we designed a reporter gene assay comprising two cell lines, namely, CHO-CD112-CD3 scFv, which stably expresses CD112 (PVRL2, nectin-2) and a membrane-bound anti-CD3 single-chain fragment variable (scFv) as the target cell, and Jurkat-NFAT-TIGIT, which stably expresses TIGIT as well as the nuclear factor of activated T-cells (NFAT) response element-controlled luciferase gene, as the effector cell. The anti-CD3 scFv situated on the target cells activates Jurkat-NFAT-TIGIT cells through binding and crosslinking CD3 molecules of the effector cell, whereas interactions between CD112 and TIGIT prevent activation. The presence of anti-TIGIT mAbs disrupts their interaction, which in turn reverses the inactivation and luciferase expression. Optimization and validation studies have demonstrated that this assay is superior in terms of specificity, accuracy, linearity, and precision. In summary, this reliable and effective reporter gene assay may potentially be utilized in lot release control, stability assays, screening, and development of novel TIGIT-targeted therapeutic antibodies.

Dendritic cell-based cancer vaccines (DC vaccines) have been proved efficient and safe in immunotherapy of various cancers, including melanoma, ovarian and prostate cancer. However, the clinical responses were not always satisfied. Here we proposed a novel strategy to prepare DC vaccines. In the present study, a fusion protein SNU containing a secretin-penetratin (SecPen) peptide, NY-ESO-1 and ubiquitin was designed and expressed. To establish the DC vaccine (DC-SNU), the mouse bone marrow-derived DCs (BMDCs) were isolated, pulsed with SNU and maturated with cytokine cocktail. Then peripheral blood mononuclear cells (PBMCs) from C57BL/6 mice inoculated intraperitoneally with DC-SNU were separated and cocultured with MC38/MC38

Objective To compare the biomechanical characteristics of new assembly of locking compression plate (NALCP) and locking compression plate (LCP) in internal fixation of femoral shaft comminuted fractures.Methods The preparation of a femoral shaft wedge fracture model (AO type 32-C2.1),six pairs of (12) femoral specimens were collected and divided into two groups randomly,with six in each group.The Group A was made up of the new assembly of locking compression plate fixation model (NALCP),and Group B the locking compression plate fixation model (LCP).The biomechanical properties of steel plates in two groups were tested by axial loading and torsional loading tests.The relative maximum displacement of fracture blocks in two groups on the X,Y and Z axes (the coronal axis was set as X axis,through the medial and lateral femur;the transverse axis was set as Z axis,through the femoral intercondylar fossa,perpendicular to the X axis;the sagittal axis was set as Y axis,perpendicular to the X and Z axis),the maximum strain,and the average strain of the steel plate were recorded.Strain distribution nephogram was produced,and the axial loading fatigue test results of Group A were recorded.Results Axial loading test:the relative maximum displacement of fracture in Group A on X,Y and Z axis were smaller than those in Group B (P ＜0.05 or 0.01);the main strain of Group A was greater than that of Group B (P ＜0.01);there was no significant difference in the average strain between Group A and Group B (P ＞ 0.05).Torsional loading test:The relative maximum displacement of fracture in Group A on X and Z axis was smaller than that of Group B (P ＜ 0.01);there was no statistically significant difference between the two groups on the Y axis (P ＞ 0.05);the main strain of plate in Group A was greater than that in Group B (P ＜ 0.01);there was no statistically significant difference in the average strain between Group A and Group B (P ＞ 0.05).There was no obvious difference in strain distribution between the two groups.In Group A,the fatigue test of axial cyclic loading was performed for 1 million times,and the NALCP was intact without deformation,loosening,or rupture.Conclusion NALCP can provide strong mechanical stability for comminuted femoral fracture.The design of bridge steel plate is reasonable,which can effectively avoid stress concentration,reduce the stress shielding of steel plate,and facilitate bone healing.

Objective To compare the stress and its distribution between our self-designed new assembly of locking compression plate (NALCP) of low elastic modulus versus conventional locking compression plate (LCP) in fixation of femoral comminuted fractures.Methods Six pairs of cadaveric femur were used to create models of middle femoral comminuted fracture.The femoral fracture models were fixated respectively by NALCP of Ti2448 with low elastic modulus (E =30 Gpa) (NALCP group) and conventional LCP of Ti-6Al-4V with high elastic modulus (E =110 Gpa) (LCP group).Axial and torsion loads were applied on the models in the 2 groups to simulate those on one leg when a person slowly walks.The relative maximum displacements on the X,Y and Z axes of fracture fragments,and the maximum and average strains of the plate were recorded in the 2 groups.Nephograms of strain distribution were made for the 2 groups.The results of fatigue test under axial loads were recorded for NALCP group.Results Both the axial and torsion loading tests showed significantly larger principal and average strains in NACLP group than in LCP group (P ＜ 0.05).However,there were no significant differences between the 2 groups in the relative maximum displacements of fracture fragments on X,Y or Z axis (P ＞ 0.05).The plate strain nephograms for the 2 groups showed consistent strain distributions.The plates in NALCP group survived 1,000,000 fatigue tests under axial loads,without any deformation,loosening or breakage.Conclusion As our NALCP of low elastic modulus may be better in stress transmission and distribution,it can effectively reduce the effect of stress-shielding and promote bone healing.

Objective:To analyze the dental and mandibular asymmetry of adults with Class Ⅱ subdivision malocclusion.Methods:The jaw bones of 30 adults with Class Ⅱ subdivision malocclusion(case group)and 30 with normal-occlusion(control group)were scanned by CBCT.Linear and angular comparison was conducted between the two groups.Results:Dental midline deviation was ob-served in case group,mostly in mandibular arch (60%).The development of Class Ⅱ molar relationship correlated mainly to distally positioned mandibular molar on Class Ⅱ side.Conclusion:In the adults with Class Ⅱ subdvision malocclusion odontogenic asymme-try is the major factor,bony asymmetry is the miner.

Objective:To analyse the asymmetry of mandibular of adults with skeletal classⅢmalocclusion and mandibular deviation using cone-beam computerized tomography(CBCT).Methods:20 adults with skeletal classⅢmalocclusion and mandibular deviation (deviation group)and 20 adults with individual normal occlusion(normal group)were included.CBCT slices were taken for each sub-ject.INVIVO 5 software was used to make 3D reconstruction and location marks for line distance and volume measurements of mandi-ble and condyle.Results:The measurements of the mandibular ramus length,mandibular total length,hemi-mandibular volume, mandibular ramus volume,posterior part of mandibular body length,condylar unit length,angular unit length,body unit length and an-gular angle in deviation group were significantly different between 2 sides(P<0.05).Compared with the normal group,differences of the asymmetry of mandibular ramus length,mandibular total length,hemi-mandibular volume,mandibular ramus volume,posterior part of mandibular body length,angular angle,condylar unit length and body unit length between 2 sides in deviation group were sig-nificantly different(P<0.05).Conclusion:In adults with skeletal classⅢmalocclusion and mandibular deviation deviated condylar and mandibular ramus are smaller than those of the nondeviated;the posterior part of mandibular body is slightly asymmetric while the anterior part of mandibular body is almost symmetric.

Objective To evaluate the morphology and position of condylar processes in skeletal Class Ⅲ adult patients with mandibular deviation.Methods Twenty skeletal Class Ⅲ adult patients with mandibular deviation were selected as the deviated group and twenty adults with normal occlusion were selected as the control group.Cone-beam CT(CBCT) scans of their temporomandibular joints were taken.The original data were reconstructed and rebuilt.A series of measurements of the condylar morphology and location were performed.The collected data were analyzed using paired t-test.Results In the deviated group,the deviated sides were smaller than the contralateral sides in the perpendicular height,volume,maximum area of axial plane and the height of condylar head.The contralateral condyle was positioned more posteriorly and laterally [(0.35 ± 0.10) and (0.58 ± 0.18) mm] than the deviated condyle (P＜0.05).Conclusions Adult skeletal Class Ⅲ patients with mandibular deviation hadsome extent of condyle asymmetry in both morphology and location.

Objective To compare the ultra-microscopic changes of periodontal Ruffini's corpuscle induced by different patterns of tooth movement,and investigate the influence of different changes of the periodontal mechanical environment on the periodontal mechanoreceptor.Methods Thirty-two eight-weeks-old SD rats were divided into control group(n=4),none-extraction group(n=12) and extraction group(n=12),and none-extraction group and extraction group were further divided into three subgroups,namely 3 day and 14 day and 28 day.For control group,no intervention was performed.For none-extraction group and extraction group,the following interventions were conducted.In none-extraction group,the maxillary left and mandibular right third molars were moved distally.In extraction group,the maxillary left third molar was moved distally,and the bilateral mandibular third molars were extracted.The ultra-structures of periodontal Ruffini's corpuscle in the periodontal ligament of the distal root of the bilateral maxillary third molars were observed under the transmission electron microscope.Results The ultra-structrural changes in the none-extraction group were mainly characterized by degeneration or abnormal distribution of mitochondria in the axon terminal,which were almost recovered at 28 d.In the extraction group,the changes were mainly characterized by deficiency or abnormal elongation of the Schwann sheath and were not recovered at 28 d.Conclusions The ultra-structures of periodontal Ruffini's corpuscle might be influenced by tooth movement and occlusal changes,and the mechanorecepting function of it might be affected by changes of the periodontal mechanical environment.