ObjectiveTo investigate the effect of interleukin (IL)-23 receptor (IL-23R) overexpression on the balance of T helper 17 (Th17 cells)/regulatory T cells (Treg cells) in experimental autoimmune uveitis (EAU) mice. MethodsTwelve 8-week-old female C57BL/6J mice were randomly divided into LV-Ctrl group and LV-IL-23R group, with 6 mice in each group. Two groups of mice were injected with LV-Ctrl and LV-IL-23Rlentiviruses through the tail vein, respectively; 7 days after injection, the EAU mouse model was established by active immunization with vitamin A-binding protein 1-20 between photoreceptors. Starting from 13 days after immunization, the fundus of the mice was observed by indirect ophthalmoscopy every 2 days and clinical scores were performed; 30 days after immunization, hematoxylin-eosin staining was used to observe the histopathological changes of mouse retina. The levels of IL-17 in serum of the two groups of mice were detected by enzyme-linked immunosorbent assay; the proportion of Th17 cells and Treg cells was detected by flow cytometry. The relative mRNA expression of IL-23R, IL-17, retinoic acid-related orphan receptor γt (RORγt), IL-10 and forkhead transcripyion factor p3 (Foxp3) were detected by real-time quantitative polymerase chain reaction. Comparisons between groups were performed using repeated measures analysis of variance, independent samples Mann-Whitney U test, and independent samples t test. ResultsCompared with the LV-Ctrlgroup, the retinal inflammatory reaction of the LV-IL-23R group was more severe. At 13 days after immunization, there was no significant difference in fundus inflammation scores between LV-IL-23R group and LV-Ctrl group (t=－2.001, P=0.058); 15-29 days after immunization. The fundus inflammation scores of LV-IL-23Rgroup were higher than those of LV-Ctrl group, and the difference was statistically significant (t=－4.429, －6.578, －7.768, －10.183, －6.325, －7.304, －4.841, －6.872; P＜0.001). Histopathological examination showed that the infiltration of inflammatory cells in the fundus increased, the retinal structure was damaged more seriously, and the histopathological score was significantly increased, and the difference was statistically significant (t=－4.339, P=0.001). Compared with the LV-Ctrl group, the relative expression of IL-23RmRNA in the spleen of the LV-IL-23R group was significantly increased, and the difference was statistically significant (Z=2.087, P=0.037). The relative expression of IL-17 and RORγt mRNA increased, while the relative expression of IL-10 and Foxp3 mRNA decreased, and the differences were statistically significant (t=－6.313,－5.922, 4.844, 7.572; P=0.003, 0.004, 0.008, 0.002). Compared with the LV-Ctrl group, the level of IL-17 in the serum of the mice in the LV-IL-23R group was significantly increased, and the difference was statistically significant (t=－5.423, P=0.002); the proportion of Th17 cells in the spleen and lymph nodes was significantly increased, whereas, the proportion of Treg cells was significantly reduced, and the difference was statistically significant (t=－4.290, 3.700; P=0.002, 0.006). ConclusionIL-23R overexpression can promote Th17/Treg imbalance in EAU mice, and aggravate the clinical and pathological manifestations of EAU.
Objective To investigate the change of the femoral offset and hip center of rotation (COR) after using Jumbo cups in total hip arthroplasty (THA) revision. Methods The clinical data of 23 patients who underwent THA revision using Jumbo cups between January 2010 and May 2015 were retrospectively analyzed. Morselized bone graft was performed on 8 cases, morselized bone graft combined with structural bone graft on 10 cases. There were 10 males and 13 females, aged 65.4 years on average (range, 51-77 years). The disease duration was 1-24 years (mean, 8.57 years). The reasons for revision included aseptic loosening in 21 cases and periprosthetic infection in 2 cases. The Harris hip score and visual analogue scale (VAS) were 43.04±5.05 and 5.70±0.97 before operation respectively. According to the Paprosky acetabular defect classification, there were 5 cases of type I, 5 cases of type II A, 3 cases of type II B, 6 cases of type II C, and 4 cases of type III A. The X-ray films showed that the femoral offset was (40.65±4.09) mm for normal side and was (44.04±5.08) mm for affected side at preoperation, showing significant difference (t=4.098,P=0.000). Ten patients underwent femoral offset reconstruction (43.48%) but 13 patients did not (56.52%) before operation. The COR was reconstructed in 10 cases (43.48%); COR elevation was observed in 11 cases (47.83%), and COR decline in 2 cases (8.69%) before operation. Results Primary healing of incision was obtained in all patients, with no complication of infection, vascular injury, deep vein thrombosis, dislocation of the joint, or fracture around prosthesis. All the patients were followed up 12-76 months (mean, 22.48 months). The Harris hip score and VAS were 82.09±4.53 and 0.74±0.62 at 1 year after operation respectively, showing significant differences when compared with preoperative scores (t=37.831,P=0.000;t=22.318,P=0.000). The X-ray films showed that the femoral offset was (43.87±3.57) mm for affected side at 1 year after operation, showing no significant difference when compared with preoperative one (t=0.250,P=0.805), but significant difference was found between affected side and normal side (t=5.591,P=0.000). The femoral offset was restored in 16 patients (69.57%) and was not restored in 7 patients (30.43%) after operation. The COR was restored in 15 patients (65.22%) and was not restored in 8 patients (34.78%). Conclusion Using Jumbo cups or combined with morselized or structural bone graft is effective in restoring hip COR and femoral offset at the maximum limit in THA revision, with good short-term outcome and improved stability of acetabular prosthesis.
目的总结左胸骨旁小切口微创封堵分流方向偏向流出道的室间隔缺损（VSD）的初步经验。 方法2014年2～8月广州医科大学附属第一医院对15例分流方向偏向流出道的VSD患者施行左胸骨旁小切口微创封堵手术，其中男7例，女8例；年龄10个月～19岁（4.5±4.6）岁；体重5.5～54.0（14.6±14.1）kg；其中干下型6例，嵴内型6例，膜周部型3例；缺损直径2.5～6.5（4.0±1.2）mm，距主动脉瓣环距离≤1 mm 9例，≤2 mm4例，>2 mm 2例；合并主动脉瓣右冠瓣轻度脱垂5例；采用左胸骨旁第2或第3肋间1.5～2.5 cm切口，在经食管超声心动图（TEE）监视下在右心室流出道表面选择适当的穿刺点，建立VSD输送轨道并置入封堵器，观察有无残余分流、主动脉瓣反流；术后3个月复查经胸超声心动图。 结果15例均成功封堵，无中转开胸，无残余分流和心律失常，新发主动脉瓣轻微反流2例，围手术期输血1例；手术时间30～120（58±28）min，术中出血量5～200（26±50）ml；术后住院时间3～13（4.3±2.6）d，无二次开胸止血、Ⅲ°房室传导阻滞、主动脉瓣反流加重、溶血、切口感染等并发症；术后3个月返院复查经胸超声心动图13例，无新发主动脉瓣反流和封堵器脱落；2例术中新发主动脉瓣反流加重，其中1例出现残余分流。 结论左胸骨旁小切口封堵分流方向偏向流出道VSD 手术安全、切口小、操作简单，近期效果尚满意；对合并主动脉瓣轻度脱垂VSD 需慎重施行外科微创封堵手术。
Objective To observe and explore the effects of adipose-derived stem cells (ADSCs)-hyaluronic acid (HA) composite on heal ing of wound combined with radiation injury. Methods The ADSCs were harvested from the fat tissue in groin of 10 inbred Sprague Dawley (SD) rats and were isolated and cultured by enzyme digestion. The ADSCs-HA composite wasprepared with ADSCs (5 × 106 cells/mL) at passage 6 and HA (10 mg/mL). Thirty inbred SD rats, 15 males and 15 females, were randomly divided into groups A (n=10), B (n=10), and C (n=10). A 2 cm × 2 cm full-thickness skin defect was made on the rat back before 20 Gy 60Co radiation exposure. One week after debridement, wounds were treated by petrolatum gauze in group A as the control group, by HA (0.4 mL) and petrolatum gauze in group B, and by ADSCs-HA composite (0.4 mL) and petrolatum gauze in group C. The microvessel density (MVD) and the distribution of CD90 positive cells were observed at 1st, 2nd, 3rd, and 4th weeks. Results The wound heal ing was slower, and wound did not heal at 4th week and still filled with granulation tissue in group A; the wound heal ing of group B was faster than that of group A, and the wound did not heal completely with depression in the center at 4th week; the wound healed completely with epidermil izated surface and no obvious depression at 4th week in group C. The histological observation showed that MVD was significantly higher in group C than in groups A and B at the 1st, 2nd, and 3rd weeks (P lt; 0.05), and in group B than in group A at the 3rd week (P lt; 0.05); MVD was significantly higher in groups B and C than in group A (P lt; 0.05), but no significant difference was found between groups B and C (P gt; 0.05) at 4th week. No CD90 positive cell was found in groups A and B; CD 90 positive cells were observed in group C and gradually decreased with time. Conclusion ADSCs-HA composite can accelerate heal ing of wound combined with radiation injury by promoting and controll ing wound angiogenesis.
ObjectiveTo summarize the biomarkers related to the efficacy of immune checkpoint inhibitors for hepatocellular carcinoma (HCC).MethodReviewed and summarized the literatures on the basic and clinical application of biomarkers related to programmed cell death protein 1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors and their combination with targeted therapy.ResultsThe combination of immunotherapy and targeted therapy had brought great hope for the treatment of patients with advanced HCC, but there were still some patients who could not benefit from it. Recent studies had shown that expression of PD-L1 in tumor tissue, tumor mutational burden, tumor-infiltrating lymphocytes, peripheral immune cells, circulating tumor DNA, gut microbiome, and so on, could predict the efficacy of immunotherapy or targeted therapy combined with immunotherapy for HCC.ConclusionsThere is no specific biomarker to predict the efficacy of immunotherapy and its combination regimen for HCC. More prospective studies are needed to confirm the predictive value of these biomarkers and to establish a multi-factor predictive model or immune score to screen patients who may benefit, which is of great significance for precise immunotherapy of HCC.