Immunogenicity and efficacy of a bivalent DNA vaccine containing LeIF and TSA genes against murine cutaneous leishmaniasis

There is no effective vaccine for the prevention and elimination of leishmaniasis. For this reason, we assessed the protective effects of DNA vaccines containing LeIF, TSA genes alone, or LeIF–TSA fusion against cutaneous leishmaniasis pEGFP‐N1 plasmid (empty vector) and phosphate buffer saline (PBS) were used as control groups. Therefore, cellular and humoral immune responses were evaluated before and after the challenge with Leishmania major. Lesion diameter was also measured 3–12 weeks after challenge. All immunized mice with plasmid DNA encoding Leishmania antigens induced the partial immunity characterized by increased IFN‐γ and IgG2a levels compared with control groups (p < 0.001). Furthermore, the immunized mice showed significant reduction in mean lesion sizes compared with mice in empty vector and PBS groups (p < 0.05). The reduction in lesion diameter was 29.3%, 34.1%, and 46.2% less in groups vaccinated with LeIF, TSA, and LeIF‐TSA, respectively, than in PBS group at 12th week post infection. IFN/IL‐4 and IgG2a/IgG1 ratios indicated that group receiving LeIF–TSA fusion had the highest IFN‐γ and IgG2a levels. In this study, DNA immunization promoted Th1 immune response characterized by higher IFN‐γ and IgG2a levels and also reduction in lesion size. These results showed that a bivalent vaccine containing two distinct antigens may induce more potent immune responses against leishmaniasis.     

In vitro study of a modified sagittal split osteotomy fixation technique of the mandible: a mechanical test

This study was performed to evaluate the compressive mechanical strength of rigid internal fixation (RIF) using 1.5-mm L-shaped plates fixed with monocortical screws in sagittal split osteotomy (SSO). Thirty synthetic hemimandibles, which had all undergone a 5-mm advancement, were divided into three groups: three 12-mm bicortical titanium screws were placed in an inverted L pattern in group A; one straight 2.0-mm system spaced titanium plate fixed with four 5-mm monocortical screws was used in group B; two 1.5-mm system L-shaped titanium plates, each fixed with four 5-mm monocortical screws, were used in group C. The models were subjected to compressive and progressive mechanical tests with forces applied in the area between the second premolar and first molar to verify resistance in Newtons (N). A displacement speed of 1 mm/min was applied, with a maximum 10 mm displacement of the distal segment or until disruption of the fixation. The deformity and/or eventual rupture of the plates were evaluated, and consequently their technical stability was determined. The results showed that the modified fixation technique tested in this study on synthetic mandibles resulted in adequate stability and superior mechanical behaviour compared to simulated osteosynthesis with the use of a straight 2.0-mm titanium plate.     

Acquired MET D1228N Mutations Mediate Crizotinib Resistance in Lung Adenocarcinoma with ROS1 Fusion: A Case Report

Patients with non‐small cell lung cancer (NSCLC) containing ROS1 fusions can have a marked response to the ROS1‐targeted tyrosine kinase inhibitors (TKIs), such as crizotinib. Common resistance mechanisms of ROS1‐fusion targeted therapy are acquired mutations in ROS1. Along with the use of next‐generation sequencing in the clinical management of patients with NSCLC during sequential targeted therapy, many mechanisms of acquired resistance have been discovered in patients with activated tyrosine kinase receptors. Besides acquired resistance mutations, bypass mechanisms of resistance to epidermal growth factor receptor (EGFR)‐TKI treatment are common in patients with EGFR mutations. Here we describe a patient with metastatic lung adenocarcinoma with CD74‐ROS1 fusion who initially responded to crizotinib and then developed resistance by the acquired mutation of D1228N in the MET kinase domain, which showed short‐term disease control for cabozantinib.Key Points

• The D1228N point mutation of MET is an acquired mutation for crizotinib resistance.
• The patient obtained short‐term clinical benefit from cabozantinib therapy after resistance to crizotinib.
• The clinical use of next‐generation sequencing could maximize the benefits of precision medicine in patients with cancer.

     

Nutritional intervention during maxillomandibular fixation of jaw fractures prevents weight loss and improves quality of life

Maxillomandibular fixation (MMF) for the management of jaw fractures leads to compromised nutritional intake and consequent weight loss and poor quality of life (QoL). The present study aimed to evaluate the effectiveness of a home-based dietary plan to prevent weight loss, and its effect on the QoL of patients who underwent four weeks of MMF for the treatment of maxillofacial fractures. A total of 50 patients were randomised into nutritional intervention (Group1) and non-intervention groups (Group 2). Patients in Group1 were counselled by a dietitian and given a diet plan. Patients in Group 2 were advised to take a liquid diet of their own choice in the form of shakes, juices, and milk, along with protein supplements. Patients in Group1 lost significantly less weight than those in Group 2 (p=0.001) at week four of follow up. Group1 patients had significantly better oral health-related QoL in the ‘physical pain’ domain during the two weeks of MMF, and in the ‘physical discomfort’ and ‘psychological disability’ domains two weeks after the release of MMF. They had significantly better nutrition-related QoL in all the domains during the two weeks of MMF and, except for the ‘physical’ domain, also during the two weeks after its release. Individual home-based diet plans effectively helped the patients maintain their weight and improved QoL.     

Fixation of subcondylar fractures of the mandible: a randomized clinical trial comparing one trapezoidal plate with two miniplates

Subcondylar fracture of the mandible accounts for 25–35% of all mandibular fractures. In the past, most subcondylar fractures were managed non-surgically. The traditional method of fixation for subcondylar fractures uses two miniplates; however some bench studies have reported that trapezoidal plates are superior. The aim of this study was to compare the outcomes of subcondylar fractures fixed either with two non-parallel straight miniplates or with one trapezoidal plate. A randomized clinical trial was designed and implemented. Fifty-two consecutive patients with subcondylar fractures were recruited. All patients underwent surgery via a retromandibular approach. The time taken for fixation of the plate after fracture reduction and postoperative outcomes and complications were compared between the groups. The trapezoidal plates were superior in terms of ease of adaptation and time taken for fixation (P =  0.0001). Plate fracture was observed only in the two miniplates group, in four (16%) patients. Outcomes were similar in the two groups in terms of occlusion, mouth opening, protrusion, and lateral excursion. In conclusion, both systems – two miniplates and the trapezoidal plate – provide functionally stable fixation. The outcome was significantly better for the trapezoidal plate than for two miniplates regarding the time taken for insertion and ease of adaptation, but not for other parameters.     

MIPPO结合NCB万向锁定板在老年股骨转子间骨折的运用

目的探讨运用MIPPO(微侵入钢板插入技术)结合NCB万向锁定板在老年股骨转子间骨折的治疗效果。方法运用MIPPO结合NCB万向锁定板对2013年7月至2015年10月收治的35例老年转子间骨折患者进行治疗,男21例,女14例;右髖16例,左髖19例;年龄为68~92岁,平均年龄83.5岁,Evans分型Ⅰ型2例,Ⅱ型5例,Ⅲ型11例,Ⅳ型10例,Ⅴ型7例。术前对患者均行骨盆正蛙位X光片和CT扫描,记录患者的手术时间、术中出血量、并发症情况、骨折愈合时间及末次随访时髖关节Harris评分等,初步分析该方法治疗老年股骨转子间骨折疗效和经验。结果本组患者手术时间平均为50.2 min(40~65 min),术中出血量平均为180 m L(150~230 m L)。35例患者术后均获得平均15.6个月(12~39个月)随访,1例出现术后内固定松脱后再行半髖置换治疗,34例术后均获得骨性愈合,平均愈合时间7.8个月(6~9个月)。术后末次随访时34例患者髖关节Harris评分平均为84.5分(75~90分)。结论 MIPPO结合NCB万向锁定板对于老年股骨转子间骨折治疗是有效、可靠的治疗方法,特别对于骨质疏松型股骨转子间骨折,微创MIPPO结合NCB万向锁定板可以达到更好的复位和早期稳定,是对老年股骨转子间骨折微创治疗方法的有益探索。