Temporal Assessment of Protein Stability in Dried Blood Spots.

The use of protein biomarkers in blood for clinical settings is limited by the cost and accessibility of traditional venipuncture sampling. The dried blood spot (DBS) technique offers a less invasive and more accessible alternative. However, protein stability in DBS has not been well evaluated. Herein, we deployed a quantitative LC-MS/MS system to construct proteomic atlases of whole blood, DBSs, plasma, and blood cells. Approximately 4% of detected proteins' abundance was significantly altered during blood drying into blood spots, with overwhelming disturbances in cytoplasmic fraction. We also reported a novel finding suggesting a decrease in the level of membrane/cytoskeletal proteins (SLC4A1, RHAG, DSC1, DSP, and JUP) and an increase in the level of proteins (ATG3, SEC14L4, and NRBP1) related to intracellular trafficking. Furthermore, we identified 19 temporally dynamic proteins in DBS samples stored at room temperature for up to 6 months. There were three declined cytoskeleton-related proteins (RDX, SH3BGRL3, and MYH9) and four elevated proteins (XPO7, RAN, SLC2A1, and SLC29A1) involved in cytoplasmic transport as representatives. The instability was governed predominantly by hydrophilic proteins and enhanced significantly with an increasing storage time. Our analyses provide comprehensive knowledge of both short- and long-term storage stability of DBS proteins, forming the foundation for the widespread use of DBS in clinical proteomics and other analytical applications.

MSCT 3D Analysis of Nasopharyngeal Airway After Le Fort I Maxillary Setback Surgeries.

In recent years, maxillary Le Fort I osteotomy setback has been widely applied in correcting maxilla prognathism. In the meantime, airway considerations have attracted more and more attention. The aim of this research was to observe the alteration of nasopharyngeal airway indexes after maxilla setback and offer evidence for the effectiveness and safety of maxillary Le Fort I setback surgeries. As for a retrospective cross-sectional study, 40 patients diagnosed with maxilla prognathism and undergoing maxillary setback surgeries were enrolled. They were grouped by the type of maxillary setback operations as group A (integral maxillary setback, n=19) and group B (segmental maxillary setback, n=21). Multislice computed tomography data were collected 1 week before (T0) and more than 3 months (T1) after surgery. 3D reconstruction and evaluation of the pharyngeal airway were conducted to analyze nasopharyngeal airway index variation before and after surgery and the difference between group A and group B. Preoperative and postoperative nasopharyngeal airway volume showed no statistical significance in group A (P=0.872) and group B (P=0.169) as well as other indexes of the nasopharynx. The comparison of postoperative airway changes between group A and group B also showed no significant difference. Both integral and segmental maxillary Le Fort I osteotomy setbacks have slight impact on nasopharyngeal airway dimensions and are safe within a specific setback range.

The effects of aligner anchorage preparation on mandibular first molars during premolar-extraction space closure with clear aligners: A finite element study.

INTRODUCTION: This study aimed to determine the effectiveness of different aligner anchorage preparations on mandibular first molars during premolar-extraction space closure with clear aligners and to assess the effects of different modes of Class II elastics on mandibular first molars. METHODS: Finite element models were constructed on the basis of cone-beam computed tomography data from an orthodontic patient. The models comprised maxilla, mandible, maxillary and mandibular teeth without first premolars, periodontal ligaments, attachments and aligners. Tooth displacement tendencies were calculated using different aligner anchorage preparations and Class II elastics on the models from the same patient. Three group sets were designed on the basis of the positions of aligner cutouts and buttons (mesiobuccal, distobuccal and lingual). Four groups were established in each of the 3 group sets. Four groups were created: (1) no elastic traction + no anchorage preparation, (2) anchorage preparation only, (3) elastic traction only, and (4) elastic traction + anchorage preparation. Different aligner anchorage preparations (0°, 1°, 2°, 3°) were applied on mandibular second premolars and molars. The Class II traction force was set to 100 g. RESULTS: With clear aligners, mandibular first molars were subject to mesial tipping, lingual tipping and intrusion. In the condition of no elastic traction, aligner anchorage preparation resulted in distal tipping, buccal tipping, and extrusion effect on mandibular first molars. Aligner anchorage preparation was more effective in the distal and lingual cutout groups than in the mesial cutout group. In the condition of Class II elastic traction, the bodily movement of mandibular first molars was achieved with a 3° anchorage preparation for the mesial cutout group and a 1.7° anchorage preparation for distal and lingual cutout groups. Absolute maximal anchorage was achieved with a 2° anchorage preparation for distal and lingual cutout groups. CONCLUSIONS: Clear aligner therapy caused mesial tipping, lingual tipping and intrusion of mandibular first molars during premolar-extraction space closure. Aligner anchorage preparation effectively prevented mesial and lingual tipping of mandibular molars. Distal and lingual cutout modes were more effective than mesial cutout modes in aligner anchorage preparation. For each aligner stage (0.25 mm), 1.7° aligner anchorage preparation and Class II elastics with distal or lingual cutouts led to the bodily movement of mandibular first molars, whereas 2° anchorage preparation reached absolute maximal anchorage.

Removal of Fracture Fragments in Intracapsular Condylar Fractures: An Alternative Treatment Option.

OBJECTIVE: This study aimed to explore bone remodeling after condylar fracture fragments have been removed from patients with intracapsular condylar fractures. it also evaluated whether condyle fracture removal can be used alternatively when the authors treat patients with comminuted or small pieces of fracture or in extremely difficult operations. METHODS: Records of patients who sustained intracapsular condylar fractures and treated by removal of fragments for the period of February 2013 to September 2019 were retrieved. Data about age, gender, date of injury, dates of admission and discharge, mechanism of trauma, location and pattern of fracture, other mandibular fracture, treatment methods and time of review were recorded and analyzed. Image dates of pre- and post-treatment (including the time of review) were also recorded. RESULTS: The data of a total of 103 patients ranging from 5 to 84 years old were retrieved during this study. A total of 135 sides of condylar fragments were removed. Almost all of the patients with comminuted condyle head fracture or type A fracture presented apparent shortening of the ramus height, and none of them showed osteogenesis (or new bone formation) during their follow-up. Present study only observed osteogenesis in few patients who sustained type B/C intracapsular condylar fractures during their follow-up. The younger the patient was, the longer the follow-up time was, and the higher the possibility of new bone formation was. No correlation was found between the amount of osteogenesis and follow-up time, the amount of osteogenesis was generally small, and no patient could form a new condyle head similar to the normal (or original) condyle head. Condylar hypertrophy only occurred in children. Four patients developed temporomandibular joint ankylosis. CONCLUSIONS: Removal of fracture fragments is an alternative treatment option for patients who sustained comminuted or small pieces of fracture or in extremely difficult operations.

Skeletal Maturation in Patients With Cleft Lip and/or Palate: A Systematic Review.

OBJECTIVE: The objective of this systematic review was to evaluate the evidence regarding skeletal maturation in patients with cleft lip and/or palate (CL/P) and to investigate whether the skeletal maturation is delayed in these patients. DESIGN: Systematic review. METHODS: Electronic and manual searches of scientific literature were conducted in 4 databases (MEDLINE, Embase, Cochrane Library, and Web of Science). Cohort studies that compared the skeletal maturation of patients with CL/P with that of children without CL/P were eligible for inclusion. The quality of included cohort studies was assessed using the Newcastle-Ottawa Scale. PATIENTS AND PARTICIPANTS: Patients of any sex and ethnicity with CL/P and children without CL/P were included in this systematic review. MAIN OUTCOME MEASURES: Difference in skeletal maturation between patients with CL/P and patients without CL/P. RESULTS: Thirteen retrospective cohort studies were included in this systematic review. Ten studies were considered of high quality and 3 were considered of general quality. The results of the included studies comparing skeletal maturation of patients with CL/P and children without CL/P were heterogeneous. CONCLUSION: Heterogeneity of skeletal maturation assessment methods, chronological age, sex, cleft type, and race may influence the final results of clinical studies on skeletal maturation in patients with CL/P. Overall, there is limited evidence to determine whether the skeletal maturation level of patients with CL/P is delayed compared to that of normal children. Further studies are needed to determine the skeletal maturation patterns in patients with CL/P.

2,6-diazaspiro[3.4]octan-7-one derivatives as potent sigma-1 receptor antagonists that enhanced the antinociceptive effect of morphine and rescued morphine tolerance.

Opioids are efficacious analgesics for pain treatments. However, their repeated use in large doses often leads to analgesic tolerance, which limits the clinical application. Sigma-1 receptor (σ1R) antagonists were reported to synergistically enhance the analgesic effect of mu opioid receptor (MOR) agonists without amplifying the adverse effects. Therefore, the σ1R is considered a promising drug target for pain management. Based on the recently elucidated co-crystal structure of σ1R with 4-IBP, we designed and developed a series of σ1R antagonists harboring the 2,6-diazaspiro[3.4]octan-7-one scaffold. Through a detailed structure-activity relationship study, we identified compound 32 as a potent σ1R antagonist, which significantly enhanced the antinociceptive effect of morphine and rescued morphine-induced analgesic tolerance. Our results support σ1R antagonism as a promising strategy to develop novel analgesics and highlight the therapeutic potential of compound 32 to prevent morphine tolerance.

Fracture fragment of the condyle determines the ramus height of the mandible in children with intracapsular condylar fractures treated conservatively.

This study aimed to explore and impart understanding of bone remodelling in children with intracapsular fractures treated conservatively. Records of children (less than 12 years), who sustained intracapsular fractures and treated conservatively, were retrieved consecutively for the period of March 2011 to February 2016. Data about age, gender, date of injury, dates of admission and discharge, mechanism of trauma, location and pattern of fracture, other mandibular fractures, treatment methods and time of review were recorded and analysed. Image dates of pre- and post-treatments, including date of review, were also recorded. A total of 22 patients complete their follow-up and show bone remodelling process. During their follow-up, all the displaced condylar fragments fused with the ramus stump at the displaced position. Regardless of the type of conservative procedure, both treatments cannot promote the spontaneous fracture reduction in patients with intracapsular condylar fractures. During follow-up, the absorption of the lateral process of the condyle after the closed treatment becomes close to the 'horizontal absorption', until the height (or articular surface) of the lateral condylar process dropped and aligned to the articular surface of the medial process. In children with intracapsular condylar fractures, the fracture fragment of the condyle determines the ramus height of the mandible. Closed treatment cannot restore the fracture fragment. If the height of the fracture fragments dropped remarkably, then open reduction and rigid internal fixation become more suitable.