Serum retinol-binding protein 4 is associated with insulin resistance in patients with early and untreated rheumatoid arthritis

ObjectiveRetinol-binding protein 4 (RBP4), systemic inflammation and insulin resistance (IR) are linked, yet the determinants of RBP4 and its impact on IR in rheumatoid arthritis (RA) are incompletely understood. The aim of this study was to explore the prevalence of IR in RA and investigate whether the serum levels of RBP4 were associated with IR in patients with RA.MethodsIn this study, 403 individuals with newly diagnosed and untreated RA were consecutively recruited. We calculated the Disease Activity Score assessed using 28-joint counts for swelling and tenderness (DAS28). Levels of serum RBP4, interleukin-6 (IL-6) and tumor necrosis factor (TNF) α were tested. IR was defined as Homeostasis model assessment for insulin resistance (HOMA-IR) index greater than or equal 2.40.ResultsIn those 403 patients, 68 (16.9%) were male and the median age was 43 years (IQR: 36–52). There was an evidently positive correlation between increased serum levels of RBP4 and increasing severity of RA (DAS28) (r = 0.403, P < 0.001). Furthermore, a modest positive correlation between levels of serum RBP4 and HOMA-IR score (r = 0.251; P < 0.0001) was found. Eighty-five patients (21.1%) in patients with RA were defined as IR (HOMA-IR ≥ 2.40), which was significantly higher than in normal cases (4.7%). In the patients with IR, serum levels of RBP4 were higher when compared with those in patients free-IR P < 0.001. The IR distribution across the quartiles of RBP4 ranged between 5.0% (first quartile) to 39.0% (fourth quartile), P for trend < 0.001. For each 1unit increase of RBP4, the unadjusted and adjusted risk of IR increased by 8% (OR: 1.08; 95% CI: 1.05–1.11, P < 0.001) and 5% (1.05; 1.02–1.09, P = 0.001), respectively. When RBP4 was added to the model containing established significant risk factors, AUROC (standard error) was increased from 0.768 (0.025) to 0.807(0.021). A significant difference in the AUC between the established risk factors alone and the addition of RBP4 was observed (difference, 0.039[0.004]; P = 0.02).ConclusionElevated serum levels of RBP4 were associated with increased risk of IR and might be useful in identifying RA at risk for IR and/or impaired glucose tolerance for early prevention strategies, especially in obese and women patients     

负载IL-4及BMP-2的氧化石墨烯-羧甲基壳聚糖凝胶对骨免疫和骨修复的早期影响研究

目的探讨负载 IL-4 和 BMP-2 的氧化石墨烯（graphene oxide，GO）-羧甲基壳聚糖（carboxymethyl chitosan，CMC）凝胶诱导巨噬细胞 M2 型分化及对 BMSCs 成骨分化的影响。方法取 CMC、GO 制备混合溶液后，分别添加 PBS、IL-4、BMP-2 或 IL-4+BMP-2，在交联剂作用下制备单纯或负载不同因子的 GO-CMC 凝胶支架；取单纯 GO-CMC 凝胶表征观测，包括大体、扫描电镜及傅里叶变换红外吸收光谱仪（Fourier transform infrared spectroscopy，FTIR）检测，以单纯 CMC 凝胶作为对照；取负载不同因子的 GO-CMC 凝胶行体外缓释实验。取 4～5 周龄 SPF 级 SD 雌性大鼠分离培养巨噬细胞，分别与单纯以及负载不同因子的 GO-CMC 凝胶培养，24 h 后行 CD206 免疫荧光检测巨噬细胞分化情况；取第 3 代大鼠 BMSCs 分别与单纯以及负载不同因子的 GO-CMC 凝胶成骨诱导培养，10 d 后行 ALP 染色观测早期成骨，21 d 行茜素红染色观测晚期成骨。结果大体观察 GO-CMC 凝胶呈棕色、半透明状；扫描电镜观察示，GO-CMC 凝胶孔径及孔壁厚度与单纯 CMC 凝胶相似，但内壁粗糙度增加；FTIR 检测显示 CMC 发生聚合形成凝胶。体外缓释实验示 3 种负载不同因子的 GO-CMC 凝胶缓释性能相似，均呈线性缓慢释放因子。CD206 免疫荧光检测示 GO-CMC 凝胶可诱导巨噬细胞 M2 型分化，ALP 及茜素红染色示 GO-CMC 凝胶可诱导 BMSCs 成骨分化；其中负载 IL-4+BMP-2 的 GO-CMC 凝胶作用最显著（P<0.05）。 结论负载 IL-4 和 BMP-2 的 GO-CMC 凝胶可诱导巨噬细胞 M2 型分化，增强 BMSCs 成骨分化能力，为后期骨缺损修复及骨免疫调节研究提供了新的策略。     

Isolation and characterization of new human carrier peptides from two important vaccine immunogens

In the preparation of glycoconjugate vaccines in clinical practice, two highly immunogenic carrier proteins, CRM₁₉₇ and tetanus toxoid (TT), are predominantly conjugated with the capsular polysaccharides (CPSs) of bacterial pathogens. In addition, TT has long been used as an effective vaccine to prevent tetanus. While these carrier proteins play an important role in immunogenicity and vaccine design alike, their defined human major histocompatibility complex class II (MHCII) T cell epitopes are inadequately characterized. In this current work, we use mass spectrometry to identify the peptides from these carrier proteins that are naturally processed and presented by human B cells via MHCII pathway. The MHCII-presented peptides are screened for their T cell stimulation using primary CD4+ T cells from four healthy adult donors. These combined methods reveal a subset of eleven CD4+ T cell epitopes that proliferate and stimulate human T cells with diverse MHCII allelic repertoire. Six of these peptides stand out as potential immunodominant epitopes by responding in three or more donors. Additionally, we provide evidence of these natural epitopes eliciting more significant T cell responses in donors than previously published TT peptides selected from T cell epitope screening. This study serves toward understanding carrier protein immune responses and thus enables the use of these peptides in developing novel knowledge-based vaccines to combat persisting problems in glycoconjugate vaccine design.     

Mildly decreased preoperative bilirubin levels are associated with infections after shoulder and knee arthroplasty

Increasing numbers of arthroplasties are also accompanied by postoperative infections. The main purpose was to evaluate preoperative serum bilirubin levels between patients with and without infections after shoulder and knee arthroplasties. For this retrospective case-control single-center study, a total of 108 patients were extracted from a prospectively collected database. Eighteen patients with infections after shoulder (n = 8) and knee (n = 10) arthroplasty were matched by age, gender, and implant type in a 1:5-scenario to 90 patients (40 shoulders and 50 knees) without postoperative infection. Demographic data, preoperative blood parameters, and postoperative infection-related outcomes were evaluated. Total bilirubin was the only preoperative parameter significantly different between the infection (8.21 ± 3.25 μmol/L or 0.48 ± 0.19 mg/dL) and noninfection (10.78 ± 4.62 μmol/L or 0.63 ± 0.27 mg/dL; P = .014) group, while C-reactive protein and other liver parameters were similar between the groups. Significantly more controls (92.1%) had preoperative bilirubin levels above 8.72 μmol/L or 0.51 mg/dL than cases (7.9%; P = .007). The 5-year infection survival-rate was 65.6% for patients with preoperative bilirubin levels < 8.72 μmol/L or < 0.51 mg/dL and 91.2% with ≥ 8.72 μmol/L or ≥ 0.51 mg/dL. Mildly decreased preoperative bilirubin levels with a cutoff at 8.72 μmol/L or 0.51 mg/dL were significantly associated to patients with infections after shoulder and knee arthroplasty. There were no differences in other blood parameters or comorbidities between patients with infections and their matched-controls.     

臀部筋膜脂肪瓣修复坐骨结节和大转子复发性窦道型压疮

目的总结臀部筋膜脂肪瓣修复坐骨结节、大转子复发性窦道型压疮的效果。方法2018 年 2 月—2019 年 6 月，收治 12 例 13 处长期截瘫伴坐骨结节、大转子复发性窦道型压疮患者。其中男 10 例 11 处，女 2 例 2 处；年龄 46～56 岁，平均 51 岁。截瘫 10～20 年，平均 13 年；所有患者均有压疮手术史，术后 3 个月～12 年复发。其中坐骨结节处压疮 11 例，坐骨结节合并大转子处压疮 1 例。创面清创、切除窦道假性滑液囊，采用单侧或双侧臀部筋膜脂肪瓣填塞窦道，术区一期缝合闭合切口。结果术后 13 处压疮切口均Ⅰ期愈合，局部无红肿、渗液，术后 14 d 拆线出院。术后局部平坦，外观理想。术后患者均获随访，随访时间 8～24 个月，平均 14 个月。随访期间压疮均无复发。结论臀部脂肪组织丰富，利用筋膜脂肪瓣修复坐骨结节、大转子复发性窦道型压疮设计、操作简便，临床效果良好。     

NADPH oxidase inhibition rescues keratinocytes from elevated oxidative stress in a 2D atopic dermatitis and psoriasis model

Emerging evidence suggests oxidative stress plays a role in the pathophysiology of both atopic dermatitis (AD) and psoriasis (PSO). We established in vitro models of AD and PSO skin, and characterized these models in regard to their oxidative stress state. Both AD and PSO model keratinocytes exhibited elevated reactive oxygen species (ROS) levels and accumulated more DNA damage than control cells after oxidative stress induced by 250 µmol/L H₂O₂. Elevated ROS levels and DNA damage accumulation could be inhibited by the NADPH oxidase (NOX) inhibitor diphenyleneiodonium (DPI). Further, immunofluorescence analysis revealed the presence of both NOX1 and NOX4 in keratinocytes. By inhibiting NOX1, stress-related signalling cascades and elevated ROS levels could be abrogated, and survival of AD and PSO cells improved. Taken together, this study reveals that inhibition of NOX inhibition could abrogate elevated oxidative stress in a 2D model of AD and PSO.