基于网络药理学的气滞胃痛颗粒抗炎镇痛活性作用分析

目的通过网络药理学的方法预测气滞胃痛颗粒抗炎镇痛主要活性成分的作用靶点,结合中医方解配伍理论对其多成分-多靶点-多通路的作用进行分析。方法基于TCMSP中药系统生物学分析数据库收集气滞胃痛颗粒中6味中药的主要化学成分,并借助LC-MS技术对所筛成分进行分析,通过TCMSP检索和Pharmmapper软件预测获取各成分主要的作用靶标,并通过DIP数据库,利用蛋白质相互作用信息建立药物靶标与炎症疼痛靶标的关联,构建药物-靶标-疾病网络,通过网络特征分析气滞胃痛颗粒抗炎镇痛的作用靶标,阐释其抗炎镇痛的主要作用机制。结果根据网络分析,共有44个炎症疼痛靶点与气滞胃痛颗粒密切相关,其中直接作用靶点有20个,主要是对环加氧酶-2(COX-2)和诱导型一氧化氮合酶(i NOS)等蛋白酶的作用,作用机制可能与调节肿瘤坏死因子(TNF)信号通路、NOD样受体(NLR)信号通路、血管内皮生长因子(VEGF)信号通路等与炎症疼痛密切相关的信号通路有关。结论气滞胃痛颗粒抗炎镇痛作用体现了中药多成分、多靶点、多途径的作用特点,该研究为深入阐释气滞胃痛颗粒抗炎镇痛作用机制提供科学依据,并且进一步说明了中医药古方配伍理论的科学性。     

Three-dimensional finite element analysis of intramedullary nail with different materials in the treatment of intertrochanteric fractures

Intramedullary nails are the common treatment options for femoral intertrochanteric fractures. However, aseptic loosening is considered to be one of the primary forms of failure that can be caused by the stress shielding between the bone and implants. The matching in mechanical properties of implant and bone is a key issue to prevent this failure. Polyetheretherketone (PEEK) and Function-graded (FG) materials are widely used in clinical because of their excellent mechanical properties. In this study, to investigate the biomechanical behaviors of intramedullary nails made of Ti-6Al-4V alloy, Stainless Steel (SS), PEEK and two FG materials, three-dimensional finite element models of intertrochanteric fracture femur with intramedullary nail were constructed with ABAQUS. The maximum von Mises stress on the femoral fracture surface fixed by PEEK intramedullary nail was the largest, followed by FG intramedullary nail, which help stimulate bone growth and subsequently reduce fracture healing time. Compared with traditional metal intramedullary nails, PEEK and FG implants might increase von Mises stress along the same path in the proximal femur. The results showed that PEEK and FG intramedullary nails obviously changed the stress distributions in the bone and reduced stress shielding. This finding indicated that PEEK and FG intramedullary nails have the potential to become alternatives to the conventional metal intramedullary nails.     

Incidence,risk factors and clinical implications of postoperative urinary tract infection in geriatric hip fractures

IntroductionPostoperative urinary tract infection (UTI) is common in geriatric patients; however, little is known about the impact of UTI in orthopedic trauma. The present study was designed to determine the risk factors and clinical impact of postoperative urinary tract infection (UTI) in acute geriatric hip fractures.Patients and methodsGeriatric patients (≥65 years of age) undergoing hip fracture surgery were identified within the American College of Surgeons National Surgical Quality Improvement Program between 2016 and 2019. Patients presenting with UTI at the time of surgery were excluded. Baseline characteristics and outcomes were compared between patients with and without postoperative UTI. Multivariate logistic regression was performed, controlling for potential confounders.ResultsA total of 46,263 patients included in the study. Overall, 1,397 (3.02%) patients had postoperative UTI. Patients who developed postoperative UTI had higher rates of pneumonia (6.44% vs. 3.76%, p < 0.001), DVT (2.22% vs. 1.04%, p < 0.001), sepsis (7.73% vs. 0.62%, p < 0.001), and more frequently experienced postoperative hospital lengths of stay exceeding 6 days (37.94% vs. 20.33%, p < 0.001). Hospital readmission occurred more frequently in patients with postoperative UTI (24.55% vs. 7.85%, p < 0.001), but surprisingly, these patients had a lower mortality rate (1.36% vs. 2.2%, p < 0.001). Adjusted analysis demonstrated the following variables associated with postoperative UTI: age ≥ 85 (OR = 1.37, 95%CI = 1.08 - 1.73), ASA class ≥ 3 (OR = 1.59, 95%CI = 1.21 – 2.08,), chronic steroid use (OR = 1.451, 95%CI = 1.05 - 1.89), blood transfusion (OR = 1.24, 95%CI = 1.05 - 1.48), and >2 days delay from admission to operation (OR = 1.37, 95%CI = 1.05 - 1.79). Postoperative UTI was significantly associated with sepsis (OR = 7.65, 95%CI = 5.72 – 10.21), postoperative length of stay >2 days (OR = 1.83, 95%CI = 1.07 – 3.13), and readmission (OR = 3, 95%CI = 2.54 – 3.55).ConclusionsIn our study, postoperative UTI was found in 3% of geriatric hip fracture patients. Predictors of postoperative UTI were age ≥ 85, ASA class ≥ 3, chronic steroid use, blood transfusion, and time to operation > 2 days from admission. Results showed that postoperative UTI is independently associated with sepsis, postoperative length of stay beyond 2 days, and hospital readmission. To diminish the risk of UTI and its consequences, we recommend operating geriatric hip fractures in 24–48 hours after admission.     

Necroptotic TNFα-Syndecan 4-TNFα Vicious Cycle as a Therapeutic Target for Preventing Temporomandibular Joint Osteoarthritis

Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Preoperative scoring system for predicting early adjacent vertebral fractures after Balloon Kyphoplasty

BackgroundAdjacent vertebral fracture (AVF) is a major complication following Balloon Kyphoplasty (BKP). There is no scoring system for predicting AVF using only preoperative elements. The purposes of this study were to develop a scoring system for predicting early AVF after BKP based on preoperative factors and to investigate the appropriate surgical indication for BKP.MethodsOf 220 patients who underwent BKP at a single institution since 2011, 65 patients over the age of 60 who had undergone a standing whole spine X-ray preoperatively were enrolled. Factors affecting the occurrence of early AVF were examined. A scoring system was created consisting of the factors exhibiting significant differences, and the correlation between the total score and the incidence of early AVF was investigated.ResultsTwenty of the 65 patients (30.8%) had early AVF. In a univariate analysis, age, previous vertebral fracture, pelvic tilt, and Local kyphosis significantly influenced early AVF. In a multivariate logistic regression analysis, age had an odds ratio of 1.136 (95% CI 1.001–1.289), previous vertebral fractures 4.181 (1.01–17.309), and Local kyphosis 1.103 (1.021–1.191). The scoring system was set as follows: ①Age (<75 years: 0 points(P), 75years≦: 1P), ②The number of previous vertebral fractures (0: 0 P, 1: 1P, 2: 2P, 3 or more: 3P), and ③Local kyphosis (<10°: 0P, 10°≦: 1P). There was a correlation between the total score and the incidence of early AVF (r = 0.812, 1P = 0.05). The incidence of early AVF was 6.4% (2 cases/31 cases) for a score of ≦1P and 54.5% (18 cases/33 cases) for a score of ≧2P.ConclusionsThere was a correlation between the total score and the incidence of early AVF. A score of 1 point or less may represent the appropriate surgical indication for BKP.     

2015—2017年解放军总医院抗震颤麻痹药物的使用情况分析

目的 了解解放军总医院抗震颤麻痹药物的应用情况与用药趋势。方法 采用世界卫生组织（WHO）推荐的以限定日剂量（DDD）为指标的分析方法，对2015-2017年解放军总医院抗震颤麻痹药物的销售金额、用药频度（DDDs）、日均费用（DDC）及排序比（B/A）等进行统计分析。结果 普拉克索、多巴丝肼和恩他卡朋的用药金额始终处于前3位，普拉克索的用药金额逐渐上升，卡比多巴/左旋多巴的用药金额逐渐下降；DDDs排序列前2位的是多巴丝肼和司来吉兰，多巴丝肼的DDDs逐年上升，一直处于第1位；2015-2016年各种抗震颤麻痹药物的DDC较为稳定，2016-2017年各种抗震颤麻痹药物的DDC开始略有下降；除普拉克索和恩他卡朋的B/A始终小于1.00，其他抗震颤麻痹药物的B/A均在1.00以上波动。结论 解放军总医院抗震颤麻痹药物的使用较为合理，其中多巴丝肼、普拉克索和司来吉兰具有很好的市场前景。