Role and Mechanism of Maresin-1 in Acute Lung Injury Induced by Trauma-Hemorrhagic Shock.

BACKGROUND It is reported that trauma hemorrhagic shock (THS) could resulted in organ injury and is related to a high mortality rate. Maresin-1 (MaR1), a derived medium through biosynthesis, is involved in inflammatory responses. However, the mechanism of MaR1 against acute lung injury needs to be further understood. This report aimed to explore whether MaR1 had a protective effect on lung injury. MATERIAL AND METHODS We constructed a THS-induced acute lung damage rat model and then treated the rats with MaR1. We determined Evan's blue dye (EBD) lung permeability, lung permeability index, wet/dry (W/D) weight ratio, nitric oxide (NO) concentration and inducible nitric oxide synthase (iNOS) expression in lung tissue samples. The inflammation-related cytokines levels in the bronchoalveolar lavage fluid (BALF) and serum of rats were determined by enzyme-linked immunosorbent assay (ELISA). Finally, the TLR4/p38MAPK/NF-kappaB pathway was analyzed by quantitative real-time polymerase chain reaction and western blot assay. RESULTS The increased EBD ratio, lung permeability index and W/D weight ratio, NO concentration and iNOS levels were suppressed by MaR1 treatment. THS-induced over-production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in BALF and serum was suppressed by MaR1. Besides, the TLR4/p38MAPK/NF-kappaB pathway activation in THS-induced rats were inhibited by MaR1 treatment. CONCLUSIONS Our study showed that MaR1 could effectively alleviated THS-induced lung injury via inhibiting the excitation of the TLR4/p38MAPK/NF-kappaB pathway in THS-induced rats, suggesting that MaR1 might be a novel agent for lung damage treatment.

Optimal sequence of surgical procedures for hemodynamically unstable patients with pelvic fracture: A network meta-analysis.

BACKGROUND: The mortality rate of patients with hemodynamic instability due to severe pelvic fracture remains substantial and massive transfusion happens frequently. Angio-embolization, external fixation and preperitoneal pelvic packing of the pelvis are the main managements used to control bleeding in these patients. In this paper, we aimed at characterizing the rationale of these surgical managements, and placed them in optimal management algorithm to compose a new guideline. METHODS: We selected controlled trials, assessing safety of management for the intervention of hemorrhagic shock from mortality data, and assessing efficacy from volume of first 24 h blood transfusion following hospitalization. Six single and combined managements were extracted as comparison. A pairwise meta-analysis was conducted using a random effect model, and then the analysis was extended to a network meta-analysis. Pooled effect sizes were ranked and demonstrated the probability of being the best treatments for safety and efficacy. RESULTS: 13 clinical trials and 24,396 participants were identified for this analysis. The assessment of rank probability indicated that pelvic packing presented the greatest likelihood of improving safety, while external fixation was indicated most efficient among the interventions for controlling hemorrhage. CONCLUSIONS: Clinical protocols for guidelines of hemodynamically unstable pelvic fracture patients have been multidirectionally developed. We strongly support the initial application of an external fixator. Provided that patients remain hemodynamically unstable after application of an external fixation, pelvic packing is the next procedure to consider. Angio-embolization is the complementary but not alternative method of choice subsequently.

Comparison of conservative treatment outcomes for proximal humeral epiphyseal fractures in patients of different ages.

BACKGROUND: Several studies have suggested that excellent therapeutic outcomes can be achieved with conservative treatment of proximal humeral epiphyseal fractures in patients younger than 11 years old; however, the outcomes of conservative treatment for children older than 11 years are controversial. To address this problem, this study compared outcomes of conservative treatment for proximal humeral epiphyseal fractures in pediatric patients of different ages. METHODS: The patients were divided into two groups for comparative purposes based on age. Group I consisted of 34 patients who were less than 11 years old (average age: 5 years) and group II included 21 patients who were 11 years of age or older (average age: 14 years). Patients in both groups underwent conservative treatment and follow-up examination, where they first were examined with X­radiography for assessment of deformity, fracture union and loss of reduction. At the final follow-up after 2 years, patients were assessed by an interview and a detailed physical examination including the assessment of shoulder function using the Constant-Murley score. RESULTS: There were no significant differences in the grading scale of varus deformity between the two groups (P > 0.05) after immediate postreduction X­radiography; however, there were significant differences in the grading scale of varus deformity between group I and group II at the 2­year follow-up (P < 0.05). There were no significant differences between the two groups with respect to the Constant-Murley score and arm length discrepancy (P > 0.05) at final follow-up examinations. CONCLUSION: In general, the results suggested that the outcomes, as measured with radiographs, for both older and young children were comparable after immediate postreduction roentgenograms. For long-term follow-up there was a difference between the two groups and the degree of angulation and displacement might be associated with treatment outcomes for older children. Thus, these factors should be considered when treating and evaluating the outcomes for older children.

Association between BUN/creatinine ratio and the risk of in-hospital mortality in patients with trauma-related acute respiratory distress syndrome: a single-centre retrospective cohort from the MIMIC database.

OBJECTIVE: Recent studies have shown that blood urea nitrogen to creatinine (BUN/Cr) ratio might be an effective marker for the prognosis of patients with respiratory diseases. Herein, we aimed to assess the association between BUN/Cr ratio and the risk of in-hospital mortality in patients with trauma-related acute respiratory distress syndrome (ARDS). DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: 1034 patients were extracted from the Medical Information Mart for Intensive Care-III (MIMIC-III) database. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome of the study was in-hospital mortality, defined by the vital status at the time of hospital discharge (ie, survivors and non-survivors). RESULTS: Of the total patients, 191 (18.5%) died in hospital. The median follow-up duration was 16.0 (8.3-26.6) days. The results showed that high level of BUN/Cr ratio was significantly associated with an increased risk of in-hospital mortality (15.54-21.43: HR=2.00, 95% CI: (1.18 to 3.38); >21.43: HR=1.76, 95% CI: (1.04 to 2.99)) of patients with trauma-related ARDS. In patients with trauma-related ARDS that aged ≥65 years old, male and female, Onychomycosis Severity Index (OSI)>98, Revised Trauma Score (RTS)>11, Simplified Acute Physiology Score II (SAPS-II)>37 and sequential organ failure assessment (SOFA) scores≤7, BUN/Cr ratio was also related to the increased risk of in-hospital mortality (all p<0.05). The predictive performance of BUN/Cr ratio for in-hospital mortality was superior to BUN or Cr, respectively, with the area under the curve of receiver operator characteristic curve at 0.6, and that association was observed in age, gender, OSI, RTS, SAPS-II and SOFA score subgroups. CONCLUSION: BUN/Cr ratio may be a potential biomarker for the risk of in-hospital mortality of trauma-related ARDS, which may help the clinicians to identify high-risk individuals and to implement clinical interventions.

Development of a borosilicate bioactive glass scaffold incorporating calcitonin gene-related peptide for tissue engineering.

Protein delivery and release from synthetic scaffold materials are major challenges within the field of bone tissue engineering. In this study, 13-93B1.5 borosilicate bioactive glass (BSG) base paste was 3D printed to produce BSG-based scaffolds with high porosity (59.85 ± 6.04%) and large pore sizes (350-400 µm) for functionalization with a sodium alginate (SA)/calcitonin gene-related peptide (CGRP) hydrogel mixture. SA/CGRP hydrogel was uniformly filled into the interconnected pores of 3D printed BSG constructs to produce BSG-SA/CGRP scaffolds which were subject to bioactivity and biocompatibility analysis. BSG scaffolds filled with SA hydrogel underwent dissolution in simulated body fluid (SBF), resulting in the precipitation of hydroxyapatite (HA) on the borosilicate glass evidenced by scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Around 90% of CGRP was released from scaffolds after 7 days of immersion in SBF, reaching a final released concentration of 893.00 ± 63.30 ng/mL. Cellular adhesion, proliferation, and differentiation of human bone marrow mesenchymal stem cells (HBMSCs) cultured with BSG-SA/CGRP scaffolds revealed improved biocompatibility and osteogenic capabilities compared with BSG-SA scaffolds in the absence of CGRP. When subcutaneously implanted in rat models, BSG-SA/CGRP scaffolds induced low localized inflammation without causing bodily harm in vivo. Findings revealed that bioactive glass scaffolds incorporating CGRP met the scaffold requirements for bone regeneration and that the addition of CGRP promoted osteogenic differentiation where it may potentially be utilized for future regenerative applications.

[A multicenter retrospective study assessing pelvic unlocking closed reduction device for reducing unstable pelvic posterior ring disruption].

Objective: To explore the application value and effectiveness of pelvic unlocking closed reduction device for the treatment of unstable pelvic posterior ring disruption. Methods: A retrospective analysis of clinical data of 243 cases of unstable pelvic posterior ring disruption treated with pelvic unlocking closed reduction device in 13 orthopaedic trauma centers across the country between December 2018 and June 2020 was performed. There were 139 males and 104 females; the age ranged from 18 to 92 years, with an average age of 48.5 years. The cause of injury included 132 cases of traffic accident injuries, 102 cases of falling from height, and 9 cases of crushing injuries. According to AO/Orthopaedic Trauma Association (AO/OTA) classification, there were 5 cases of type 61-B1, 13 cases of type 61-B2, 32 cases of type 61-C1.1, 47 cases of type 61-C1.2, 89 cases of type 61-C1.3, 35 cases of type 61-C2, and 22 cases of type 61-C3. The time from injury to operation was 2-121 days, with a median of 10 days. Preoperative preparation time, installation time of unlocking closed reduction device, fracture reduction time, intraoperative fluoroscopy times, intraoperative blood loss, and surgical complications were recorded, and Matta scoring standard was used to evaluate the quality of fracture reduction. According to Matta evaluation results, the patients were divided into two subgroups: excellent-good group and fair-poor group. The differences in gender, age, time from injury to operation, AO/OTA classification, and perioperative clinical indicators were compared between the two groups, and the effects of baseline data and perioperative indicators on the quality of fracture reduction were studied. Results: Pelvic unlocking closed reduction device did not interfere with the display of the pelvic structure and fracture displacement direction during the intraoperative fluoroscopy, effectively correcting the displacement of the pelvic ring. The preoperative preparation time was 17-60 minutes, with an average of 30 minutes; installation time of unlocking closed reduction device was 10-32 minutes, with an average of 21 minutes; intraoperative fracture reduction time was 15-205 minutes, with an average of 49.2 minutes; intraoperative fluoroscopy times were 41-420 times, with an average of 132 times; intraoperative blood loss was 40-1 500 mL, with an average of 71.5 mL. The reduction quality of pelvic fracture was evaluated according to Matta score immediately after operation. The results were excellent in 153 cases, good in 61 cases, fair in 24 cases, and poor in 5 cases. The excellent and good rate was 88.1%. Further subgroup analysis showed that there was no significant difference in other indexes ( P>0.05) between the excellent-good group and the fair-poor group except for the time from injury to operation and AO/OTA classification ( P<0.05). Among them, the excellent-good reduction rate was 92.2% (119/129) in patients with injury-to-operation time less than 10 days, and the fair-poor reduction rate was 25.7% (9/35) and 40.9% (9/22) in patients with AO/OTA 61-C2 and 61-C3 types, respectively. There was no surgery-related complication due to the application of the pelvic unlocked reduction device, no secondary iliac fractures, vascular, or nerve injuries, and postoperative CT showed that all channel screws were located in the osseous channel. Conclusion: The pelvic unlocking reduction device can effectively help to reduce the unstable pelvic posterior ring and maintain reduction, meet the needs of different projection angles of pelvic fracture with intraoperative C-arm fluoroscopy. The system facilitate the operation of pelvic reduction and precise fixation.

[Application and research status of bioactive glass in bone repair].

OBJECTIVE: To summarize the clinical application and research status of bioactive glass (BAG) in bone repair. METHODS: The recently published literature concerning BAG in bone repair at home and abroad was reviewed and summarized. RESULTS: BAG has been widely used in clinical bone repair with a favorable effectiveness. In the experimental aspect, to meet different clinical application needs, BAG has been prepared in different forms, such as particles, prosthetic coating, drug and biological factor delivery system, bone cement, and scaffold. And the significant progress has been made. CONCLUSION: BAG has been well studied in the field of bone repair due to its excellent bone repair performance, and it is expected to become a new generation of bone repair material.

Accurate MRSA identification through dual-functional aptamer and CRISPR-Cas12a assisted rolling circle amplification.

Infectious diseases have become one of the most threatening global challenge with high morbidity and mortality, bringing great difficulties to clinical diagnosis and treatment. New strategy for high-specific and sensitive bacteria detection are urgently needed in facing the crisis of worldwide antibiotic resistance. Herein, a novel method through the integration of dual aptamer technology and CRISPR-Cas12a assisted rolling circle amplification (RCA) was present to obtain both accurate identification and high-sensitive detection of Methicillin-Resistant Staphylococcus Aureus (MRSA). The specificity inherited from the dual functionalized aptamers initiated bioconjugation to specifically recognize the protein targets on the surface of bacteria. Besides the target activity, the functionalized aptamer could also convert the protein recognition to nucleic acids signals. Through the integration of attached RCA and CRISPR-Cas12a assisted trans-cleavage, dual amplification of the nucleic acid signal was obtained. Based on this, we have extended the application of CRISPR-Cas12a from the nucleic acid detection to bacteria detection. As a result, the proposed method was demonstrated to be with significantly improved sensitivity towards MRSA detection. We believe that the novel integrated strategy would diversify the existing pool of bacterial detection and inspire the development of promising drug candidates in the future.

miRNA-155 expression and role in pathogenesis in spinal tuberculosis-induced intervertebral disc destruction.

The current study aimed to investigate microRNA-155 (miR-155) expression in spinal tuberculosis-induced intervertebral disc destruction and its regulatory role in disease pathogenesis. A total of 26 patients with intervertebral disc destruction induced by spinal tuberculosis and 31 healthy individuals were included. Reverse transcription-quantitative polymerase chain reactions, western blot analysis and ELISA were performed to detect mRNA and protein expression levels. A bioinformatics analysis was applied to predict the upstream regulator of matrix metalloproteinase (MMP)13, which was confirmed by dual-luciferase reporter assay. Compared with the control group, mRNA and protein expression levels of MMP13 were significantly increased in the intervertebral disc of patients with spinal tuberculosis. However, miR-155 expression in the intervertebral disc of patients with spinal tuberculosis was significantly decreased compared with the control group. Dual-luciferase reporter assays suggested that miR-155 bound to the 3'-untranslated region of MMP13 to regulate gene expression. In primary annulus fibrosus cells, upregulated miR-155 expression significantly decreased MMP13 expression in the cells and culture supernatant, whereas it increased type II collagen expression. Upregulated MMP13 expression in the intervertebral disc in patients with spinal tuberculosis may be correlated with downregulated miR-155 expression. miR-155 may regulate expression levels of associated proteins in the intervertebral disc via modulating MMP13 expression, which contributes to the disease pathogenesis. The results of the current study may provide the theoretical basis for the diagnosis and treatment of disc damages caused by spinal tuberculosis.

[Treatment of pediatric distal femur fractures by external fixator combined with limited internal fixation].

OBJECTIVE: To discuss the clinical effects of external fixator combined with limited internal fixation in the treatment of pediatric distal femur fractures. METHODS: From January 2008 to June 2014, 17 children of distal femur fractures were treated by external fixator combined with limited internal fixation. There were 12 males and 5 females, aged from 6 to 13 years old with an average of 10.2 years, ranged in the course of disease from 1 h to 2 d. Preoperative diagnoses were confirmed by X-ray films in all children. There were 11 patients with supracondylar fracture , and 6 patients with intercondylar comminuted fracture. According to AO/ASIF classification, 9 fractures were type A1, 5 cases were type A2,and 3 cases were type C1. The intraoperative and postoperative complications, postoperative radiological examination, lower limbs length and motion of knee joints were observed. Knee joint function was assessed by KSS score. RESULTS: All the patients were followed up from 6 to 38 months with an average of 24.4 months. No nerve or blood vessel injury was found. One case complicated with the external fixation loosening, 2 cases with the infection of pin hole and 3 cases with the leg length discrepancy. Knee joint mobility and length measurement (compared with the contralateral), the average limited inflexion was 10 degrees (0 degrees to 20 degrees), the average limited straight was 4 degrees (0 degrees to 10), the average varus or valgus angle was 3 degrees (0 degrees to 5 degrees). KSS of the injured side was (96.4 +/- 5.0) points at final follow-up, 16 cases got excellent results and 1 good. All fractures obtained healing and no epiphyseal closed early was found. CONCLUSION: External fixator combined with limited internal fixation has advantages of simple operation, reliable fixation, early functional exercise in treating pediatric distal femurs fractures.