Objective To evaluate the efficacy of a combined immunosuppression regimen in modulating rejection in genetically modified pig-to-macaque xenogeneic heart transplantation.Methods Two xenogeneic heart transplantation models were constructed using genetically modified pigs and macaques.Dynamic monitoring of recipient peripheral blood immune parameters and observation of graft pathological changes were performed.Results Regimen 1,featuring B-cell depletion,T-cell inhibition,and C3 complement suppression,reduced lymphocyte levels but failed to control acute humoral rejection and macrophage infiltration.Regimen 2,adding C5 complement inhibition and interleukin-6 inhibition to Regimen 1,more effectively lowered lymphocyte levels,inhibited acute humoral rejection and complement activation,and decreased antibody deposition.However,a late-phase cytokine storm and residual T cells emerged.Conclusions Regimen 2 reduces the hyperacute and acute rejection risks through multi-target intervention.Yet,it requires balancing medication complexity and safety.This indicates the need to optimize cellular immune regulation and adjust the plan through dynamic multidimensional monitoring.

Objective To evaluate the efficacy of a combined immunosuppression regimen in modulating rejection in genetically modified pig-to-macaque xenogeneic heart transplantation.Methods Two xenogeneic heart transplantation models were constructed using genetically modified pigs and macaques.Dynamic monitoring of recipient peripheral blood immune parameters and observation of graft pathological changes were performed.Results Regimen 1,featuring B-cell depletion,T-cell inhibition,and C3 complement suppression,reduced lymphocyte levels but failed to control acute humoral rejection and macrophage infiltration.Regimen 2,adding C5 complement inhibition and interleukin-6 inhibition to Regimen 1,more effectively lowered lymphocyte levels,inhibited acute humoral rejection and complement activation,and decreased antibody deposition.However,a late-phase cytokine storm and residual T cells emerged.Conclusions Regimen 2 reduces the hyperacute and acute rejection risks through multi-target intervention.Yet,it requires balancing medication complexity and safety.This indicates the need to optimize cellular immune regulation and adjust the plan through dynamic multidimensional monitoring.

Objective To explore the biomechanical responses of the cupula of the human semicircular canal to three basic rotational perception processes.Methods A one-dimensional visual semicircular canal model was successfully fabricated using three-dimensional printing and hydrogel physical cross-linking technologies,and the response deformation of the cupula was explored by applying constant angular velocity,constant angular acceleration,and sinusoidal oscillation stimulations.Results The time constant of the biomimetic semicircular canal model was stable at approximately 3 s and close to the human time constant.The displacement deformation of the ampullary cupula was proportional to the angular acceleration applied.Under sinusoidal oscillation stimulation of 0.07-5.00 Hz,the gain of the semicircular canal increased from 1.54 um/° rises to 42.34 μm/°,but the phase difference decreased from 109.72° to 11.27°.Conclusions The biomimetic semicircular canal model prepared in this study can accurately simulate the working mechanism of the human semicircular canal and is expected to play a role in mechanism research and disease diagnosis of the human vestibular semicircular canal.

Objective To investigate the relationship between MRI signal,pathological changes and neurological function after sciatic nerve injury in rabbits.Methods Twenty New Zealand white rabbits were randomly and evenly divided into 5 groups,and the right sciatic nerve crush models were established.T2 fat suppression fast recovery spin echo (T2 fs FRFSE) sequence scanning was performed 3 days,7 days,2 weeks,3 weeks and 4 weeks after injury,and TE was set as 30,60 and 90 ms,respectively.Signal intensity ratio (SIR) and relative signal intensity (△S) of proximal and distal part of injured nerve and control side nerve were measured.The relationship between SIR,△S,pathology and rabbit lower limb nerve function were analyzed.Results In the distal part of injured nerve,SIR and △S increased 3-7 days after injury,pathological results showed vacuolar degeneration,and basic toe function lost was found.SIR and △S reached the peak 2 weeks after injury,with most serious disintegration of myelin and toe function disable.SIR,△S and toe function disable gradually recovered,and the nerve regenerated at 3-4 weeks after injury.The injure display rate of T2 fs FRFSE images with TE=90 and 60 ms,SIR of both distal and proximal part of injured nerve were higher than those on images with TE=30 ms (all P＜0.05).Conclusion SIR and △S changes on T2 fs FRFSE imaging can be used to predict rabbit nerve injury.

Objective To explore the most effective formula to predict the catheterization length of the right internal jugular vein by an-terior approach. Methods Sixty-seven cases performed with right internal jugular vein catheterization from January 2013 to June 2013 were enrolled in this study and 4 formulas were selected to predict the catheterization lengths. Comparing their predicted lengths with the actual lengths defined as the lengths of the internal catheters which terminals were inserted to a accurate position,and analyse their predictive validi-ty. Results The predictive error percentages of the 4 formulas were all less than 15%. Comparing the predicted lengths and the actual lengths, there was no difference between the predicted length of the 1st formula and the actual one(P>0. 05),and the predicted lengths of the other three formulas were significantly less than the actual ones(P<0. 05). Comparing the mean absolute predictive errors of the 4 formu-las in the 3 height groups of 150~159 cm,160~169 cm and 170~179 cm,respectively,those of the 4th formula were all significantly higher than those of the 1st formula in all the 3 groups(P<0. 05);and no differences between those of the 2nd or the 3rd formula and those of the 1st formula were observed(P>0. 05). Conclusion The predictive error of all the 4 formulas is less than 15%, and the 1st formula is simple,practical and associated with a much smaller error,more suitable to estimate the length of the right internal jugular vein catheterization by anterior approach.

Objective To explore the effect of comorbidities on the surgical outcomes of elderly patients with hip fracture. Methods The Age,gender,weight,type of fracture,preoperative comorbidities and surgical outcomes of 117 patients aged 80 yr or over who undergoing hip fracture surgery in our hospital were recorded. Patients were divided into rehabilitation group and postoperative in-hospital death group ac-cording to surgical outcomes. The potential predictors of postoperative in-hospital death were identified by univariate model and were then entered into multiple Logistic regression analysis. Results Twenty three patients(19. 7%)had no comorbidity,94 patients(80. 3%)had one or more comorbidities. Ten patients(8. 5%)died in hospital after the operation. Predictors of postoperative in-hospital death were preoperative respiratory diseases and three or more comorbidities. Conclusion Surgical outcomes of elderly patients with hip fracture may be predicted by analysing preoperative comorbidities. Preoperative preparations must be sufficient in order to ensure successful operation.

Objective To explore the effect of recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein injection (rhTNFR:FC) on the expression of cartilage oligomeric matrix protein (COMP) in the synovial fluid and peripheral blood of juvenile idiopathic arthritis (JIA); and to explore the clinical significance of COMP for JIA and the relationship between rhTNFR:FC and COMP in JIA.Methods Thirty-five patients with JIA (JIA group),30 patients with traumatic arthritis (trauma group) and 30 patients with indirect inguinal hernia hernioplasty (normal group) were included.Peripheral blood from all enrolled patients and synovial fluid from 15 JIA and 10 trauma arthritis were obtained for COMP detection before the treatment.Fifteen JIA (group A) patients were treated with combined rhTNFR:FC,diseasemodifying antirheumatic drugs (DMARDs) and non-steroid anti-inflammatory drugs (NSAIDs),20 JIA (group B) were treated with combined DMARDs and NSAIDs.After three to six months' treatment and when the disease were in remission,peripheral blood from group A and B were drawn for COMP detection.In group A,the synovial fluid from 5 patients were obtained for COMP detection after treatment.At the same time,such as tender joint count (TJC),swollen joint count (SJC),time for morning stiffness,blood routine,erythrocyte sedimentation rate (ESR),and C-reactive protein (CRP) and other parameters before and after treatment were measured.The level of COMP was tested by double antibody sandwich enzyme-linked immunosorbent assay.The measurement data were tested for variance and independent sample t-test; and the enumeration data were tested by chi-squared or Fisher's exact test.Pearson's correlation analysis was adopted to analyze the association among the variables.Results ① The blood COMP level before treatment was (0.77±0.29) ng/ml in the JIA group,(1.00±0.28) ng/ml in the traumatic arthritis group,and (1.33±0.37) ng/ml in the normal control group.The level in the former two groups was obviously lower than that in the normal control group.The variation was statistically significant (F=25.345,P＜0.05).The comparison between any two groups was statistically significant (P＜0.05).② The COMP level in the synovial fluid before treatment were (14.8±1.6) ng/ml in the JIA group,(15.1±1.0) ng/ml in the traumatic arthritis group.The variation was not stati-stically significant (t=0.523,P=0.606).③ The serum COMP level of the systemic JIA group was obviously lower than that of the oligoarticular JIA patients,and patients with enthesitis-related arthritis and polyarticular JIA (0.26± 0.03 vs.0.87±0.17,0.89±0.22 and 0.70±0.35 ng/ml,respectively; F=9.244,P＜0.05).④ The serum COMP level of JIA at the acute phase was negatively correlated with white blood cells count (WBC),CRP and ESR (r=-0.556,-0.582 and-0.684,respectively; P all＜0.05).By contrast,no correlation was detected between the serum COMP level and joint tenderness index,joint swelling index,morning stiffness duration,hemoglobin level and platelet count(r=0.06,-0.206,-0.107,0.15 and-0.185,respectively; P all ＞0.05).⑤ The serum COMP level was obviously lower in the JIA with joint destruction than that without joint destruction (0.52±0.22 vs.0.92±0.22 ng/ml; t=5.207,P＜0.05).⑥After treatment,the blood COMP level in group A was (1.33±0.21) ng/ml and (0.96±0.22) ng/ml in group B,which was obviously higher than that in the JIA group before treatment (0.77±0.29) ng/ml.In addition,the level in group A was higher than that in group B.The variation was statistically significant (F=24.681,P＜0.05).⑦ After treatment,the COMP level in the synovial fluid (18.4± 1.1) ng/ml (n=5) was higher than that before the treatment was (14.8± 1.6) ng/ml (n =15).The variation was of statistical significant (t=4.565,P＜0.05).Conclusion The COMP level in blood and synovial fluid declines before treatment and increases after treatment.The increase is more obvious after combined with rhTNFR:FC treatment.The serum COMP level is remarkably decreased in JIA at the acute phase,systemic JIA,and the JIA with destruction of joint,and showes a negative correlation with WBC,CRP and ESR.Serum COMP may be a useful marker of active disease,destruction of joint and growth inhibition for patients with JIA.rhTNFR:FC treatment for JIA can facilitate the recovery of COMP.

Transcription factor (TF) binding to its DNA target site plays an essential role in gene regulation.The location,orientation and spacing of transcription factor binding sites (TFBSs) also affect regulatory function of the TF.However,how nu-cleosomal context of TFBSs influences TF binding and subsequent gene regulation remains to be elucidated.Using genome-wide nucleosome positioning and TF bind-ing data in budding yeast,we found that binding affinities of TFs to DNA tend to decrease with increasing nucleosome occupancy of the associated binding sites.We further demonstrated that nucleosomal context of binding sites is correlated with gene regulation of the corresponding TF.Nucleosome-depleted TFBSs are linked to high gene activity and low expression noise,whereas nucleosome-covered TFBSs are associated with low gene activity and high expression noise.Moreover,nucleosome-covered TFBSs tend to disrupt coexpression of the corresponding TF target genes.We conclude that nucleosomal context of binding sites influences TF binding affinity,subsequently affecting the regulation of TFs on their target genes.This emphasizes the need to include nucleosomal context of TFBSs in modeling gene regulation.