Modular virus-like particles for sublingual vaccination against group A streptococcus

Infection with Group A streptococcus (GAS)—an oropharyngeal pathogen—leads to mortality and morbidity, primarily among developing countries and indigenous populations in developed countries. The development of safe and affordable GAS vaccines is challenging, due to the presence of various unique GAS serotypes, antigenic variation within the same serotype, and potential auto-immune responses. In the present study, we evaluated the use of a sublingual freeze-dried (FD) formulation based on immunogenic modular virus-like particles (VLPs) carrying the J8 peptide (J8-VLPs) as a potential safe and cost-effective GAS vaccine for inducing protective systemic and mucosal immunity. By using in vivo tracing of the sublingual J8-VLPs, we visualized the draining of J8-VLPs into the submandibular lymph nodes, in parallel with its rapid absorption into the systemic circulation, which support the induction of effective immune responses in both systemic and mucosal compartments. The sublingual administration of J8-VLPs resulted in a high serum IgG antibody level, with a good balance of Th1 and Th2 immune responses. Of note, sublingual vaccination with J8-VLPs elicited high levels of IgA antibody in the saliva. The co-administration of mucosal adjuvant cholera toxin (CT) further enhanced the increase in salivary IgA antibody levels induced by the J8-VLPs formulation. Moreover, the levels of salivary IgA and serum IgG observed following the administration of the CT-adjuvanted FD formulation of J8-VLPs (FD-J8-VLPs) and non-FD formulation of J8-VLPs were comparable. In fact, the saliva isolated from mice immunized with J8-VLPs and FD-J8-VLPs with CT demonstrated opsonizing activity against GAS in vitro. Thus, we observed that the sublingually delivered FD formulation of microbially produced modular VLPs could prevent and control GAS diseases in endemic areas in a cost-effective manner.     

抗体偶联药物的临床应用及其耐药性优化对策的研究进展

抗体–药物偶联(ADC)是现代“精准医疗”需求下药学发展的必然趋势。从2000年第一款ADC药物的上市成功到2020年ADC药物的研发层出不穷。肿瘤靶向治疗的发展带动了ADC药物研发领域的快速兴起。ADC药物是使用具有特异性的单克隆抗体与具有生物活性的细胞毒素结合,将药物特异性递送至肿瘤表面位点,避免对正常细胞的杀伤,减少毒副作用。ADC为细胞毒性有效载荷提供了一种较为理想的递送方法。但是也必须清楚的认识到,由于肿瘤异质性、肿瘤代谢、肿瘤血供等多种因素导致的肿瘤耐药是ADC药物发展中所面临的一大挑战。从ADC药物的发展进程、临床应用及其所面临的耐药问题进行综述,探讨抗体偶联药物的临床应用及其所面临的挑战和策略。     

青少年前交叉韧带损伤特点及治疗选择的研究进展

青少年前交叉韧带（anterior cruciate ligament，ACL）损伤的发生率明显高于成年人，因其骨骺的闭合程度不同，治疗方案也有所不同。目前认为早期手术对于青少年ACL是积极有效的治疗方法，根据骨骺闭合情况有多种手术方式可选择，包括完全穿骺板技术、部分穿骺板技术（混合损伤）、全骨骺内技术和纯骺外技术。青少年ACL损伤应采用个体化治疗，选择一种对患者发育影响最小且有效的治疗方案。通过查阅国内外相关文献，本文总结分析了青少年ACL损伤的特点及治疗方法的选择。     

隐睾并发睾丸网腺癌1例报告并文献复习

目的:探讨1例隐睾并发睾丸网腺癌的临床病理学特征及诊治要点。方法:收集1例隐睾并发睾丸网腺癌患者的临床及影像学、观察期病理学形态及免疫表型，并复习相关文献，探讨其病理诊断和诊治要点。结果:患者老年男性，因右侧腹股沟肿痛一周入院。查体右侧腹股沟区触及实性肿块，压痛、质地较硬，右侧阴囊空虚。CT显示右侧腹股沟睾丸样肿块合并积液、腹膜转移增厚、腹水形成。病理组织学检查显示有乳头状结构，伴有腺体和小管，基质富含胶原，以实性病变为主。肿瘤细胞呈中度核异型性和频繁的核分裂。显微镜下可见曲细精管、精原细胞减少，基底膜增厚。肿瘤细胞免疫组化CEA+、CA199+、HBME-1-、EMA+、Calectin-、CK5/6-。结论:睾丸网腺癌临床罕见，病因不明，临床表现无特异性，确诊易延误。基本治疗是根治性睾丸切除术辅以根治性腹膜后淋巴结清扫术，转移性睾丸网腺癌予以化疗，放疗效果不佳。     

Evaluation of motor vehicle crashes between scooter riders and car drivers after diagnosis of type 2 diabetes in Taiwan

BackgroundDespite the plausibility that diabetes may increase the risk of motor vehicle crashes (MVCs) due to various diabetes related complications and co-morbidity, findings from epidemiological studies on the relationship between diabetes and MVCs remained inclusive mainly due to heterogeneity in the study design and failure to complete consideration of potential confounders. This study re-visited this putative association with an improved study design.MethodThis study employed a controlled before–after study design and included 1,264,280 people aged 18–75 years with T2D newly diagnosed from 2009–2014 and an equal number of age-, sex-, and time-matched controls. The rate ratios (RRs) of vehicle type–specific incidence rates of MVCs in the 1 and 2 years before and after diabetes diagnosis (or the matched dates) were compared between the individuals with type 2 diabetes (T2D) and their matched controls.ResultsThe rate of MVCs increased slightly among people with T2D over 1 and 2 years following diabetes diagnosis, with RRs of 1.04 (95% confidence interval [CI]=1.02–1.07) and 1.11 (95% CI=1.09–1.13), respectively. These RRs were comparable to those obtained for controls (1.06 and 1.12, respectively). By contrast, the RRs of scooter crashes were significantly higher in the T2D group than in the control group during the 1 year (1.28 vs. 1.08, p < 0.001) and 2 years (1.32 vs. 1.08, p < 0.001) following diabetes diagnosis.Conclusion: T2D diagnosis was associated with a moderate but significant increase in the risk of MVCs among scooter drivers, but not among car drivers.     

Modified Ni-Nail and C-Nail systems for intra-articular fractures of the calcaneus: A biomechancial study

ObjectivesWe have proposed a novel intramedullary nail (Ni-Nail) by incorporating a sustentaculum tali screw to improve the fixation stability of minimally invasive treatment for calcaneal fractures. This study aimed to evaluate the biomechanical characters of the Ni-Nail system and compare it with traditional C-Nail system.MethodsA finite element model of a Sanders type-IIIAB calcaneal fracture was reconstructed and fixed using two intramedullary nail systems, which was validated by a cadaver study. A vertical loading of 700 N was applied to the subtalar joint surfaces, and 525 N Achilles tendon tension was applied to the superior border of the Achilles tuberosity. The von Mises stresses and fracture displacements of both fixation models were evaluated.ResultsThe maximum von Mises stress of the screws of Ni-Nail and C-Nail were 27.92 MPa and 57.42 MPa, respectively, while that of the main nail were 67.44 MPa and 53.01 MPa. In addition, the maximum fracture displacement of the Ni-Nail was larger than that of C-Nail by 15.6% (0.37 mm vs.0.32 mm).ConclusionsOur static simulation analysis showed that both Ni-Nail and C-Nail demonstrated similar biomechanical stability for calcaneal fixation. The Ni-Nail features a simple structure that is easier to operate and less traumatizing. Future studies may consider to further evaluate the clinical effectiveness by clinical trials and follow-ups.     

压力引导式经皮椎体后凸成形术治疗中段胸椎骨质疏松性椎体压缩性骨折

目的 探讨压力引导式经皮椎体后凸成形术（PG-PKP）治疗中段胸椎骨质疏松性椎体压缩性骨折（OVCF）的临床疗效及骨水泥渗漏情况。方法 回顾性分析2017年1月—2019年8月采用PG-PKP和传统PKP治疗的39例中段胸椎OVCF患者临床资料。根据手术方式分为PG-PKP组（A组,20例）和传统PKP组（B组,19例）。记录所有患者术前骨密度、术中骨水泥用量、手术时间及住院时间。测量手术前后X线片上骨折节段椎体前缘高度及后凸Cobb角,评估伤椎恢复情况;在术前CT上测量手术通道影像学参数,在术后CT上观察骨水泥渗漏情况。采用疼痛视觉模拟量表（VAS）评分和Oswestry功能障碍指数（ODI）评估临床疗效。结果 所有手术顺利完成,患者随访3~12（8.64±2.84）个月。手术时间40~90（63.33±13.59）min,住院时间4~8（6.15±1.16）d。2组患者术后1 d和术后3个月的椎体前缘高度、后凸Cobb角、VAS评分、ODI较术前明显改善,差异均有统计学意义（P < 0.05）。2组骨水泥注入量和骨水泥渗漏率差异有统计学意义（P < 0.05）。A组骨水泥渗漏率为10.00%（2/20）,B组为26.32%（5/19）。术后切口均一期愈合,无骨水泥渗漏致脏器栓塞及脊髓、神经根受压等并发症发生。结论 与传统PKP相比,PG-PKP治疗中段胸椎OVCF临床疗效及影像学指标恢复满意,骨水泥渗漏率低,值得临床推广。     

AM-PAC mobility scores predict non-home discharge following adult spinal deformity surgery

BACKGROUND CONTEXTAdult spinal deformity (ASD) surgery requires an extended recovery period and often non-routine discharge. The Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility Inpatient Short Form (6-Clicks) is a prediction tool, validated for other orthopedic procedures, to assess a patient's ability to mobilize after surgery.PURPOSETo assess the thresholds of AM-PAC scores that determine non-home discharge disposition in patients who have undergone ASD surgery.STUDY DESIGNRetrospective reviewPATIENT SAMPLENinety consecutive ASD patients with ≥5 levels fused who underwent surgery from 2015 to 2018, with postoperative AM-PAC scores measured before discharge, were included.OUTCOME MEASURESNon-home discharge dispositionMETHODSPatients with routine home discharge were compared to those with non-home discharge. Bivariate analysis was first conducted to compare these groups by preoperative demographics, comorbidities, radiographic alignment, surgical characteristics, HRQOLs, and AM-PAC measurements. Threshold linear regression with Bayesian information criteria was utilized to identify the optimal cutoffs for AM-PAC scores associated with increased likelihood of non-home discharge. Finally, multivariable analysis controlling for age, sex, comorbidities, levels fused, perioperative complication, and home support was conducted to assess each threshold.RESULTSThirty-six (40%) of 90 patients analyzed had non-home discharge. On bivariate analysis, first AM-PAC score (13.5 vs. 17), last AM-PAC score (17 vs. 20), and AM-PAC change per day (+.387 vs. +1) were all significantly associated with non-home discharge. Threshold regression identified that cutoffs of ≤15 for first AM-PAC score, <17 for last AM-PAC score, and <+0.625 for daily AM-PAC change were associated with non-home discharge. On multivariable analysis, first AM-PAC score ≤15 (odds ratio [OR] 11.28; confidence interval [CI] 2.96-42.99; p<.001), last AM-PAC score <17 (OR 33.57; CI 5.85-192.82; p<.001), and AM-PAC change per day <+0.625 (OR 6.24; CI 2.01-19.43; p<.001) were all associated with increased odds of non-home discharge.CONCLUSIONSFirst AM-PAC score of 15 or less can help predict non-home discharge. A goal of daily AM-PAC increases of 0.625 points toward a final AM-PAC score of 17 can aid in achieving home discharge. The early AM-PAC mobility threshold of ≤15 may help prepare for non-home discharge, while AM-PAC daily changes per day <0.625 and final AM-PAC <17 may provide goals for mobility improvement during the early postoperative period in order to prevent non-home discharge.