Characterization of Combined Blast- and Fragment-Induced Pelvic Injuries and Hemostatic Resuscitation in Rabbits.

INTRODUCTION: To establish a blast- and fragment-induced pelvic injury animal model in rabbits, observe its injury characteristics, and explore the effects of hemostatic resuscitation combined with damage control surgery (DCS) with respect to this injury model. METHODS: Forty-eight rabbits were randomly allocated to four groups: group A rabbits were subjected to pelvic injury, group B rabbits to pelvic injury + DCS, group C rabbits to pelvic injury + DCS + resuscitation with Hextend, and group D rabbits to pelvic injury + DCS + Hextend + hemostatic resuscitation with tranexamic acid, fibrinogen concentrate, and prothrombin complex concentrate. Simulated blast and fragment-induced pelvic injury was produced by a custom-made machine. We implemented CT scanning and necropsy to assess the injury state and calculated the coefficient of variation (CV) of the cumulative abbreviated injury scale (AIS) to assess the reproducibility of the animal model. Immediately after instrumentation (0 h), and 1 h, 2 h, 4 h, and 8 h after injury, blood samples were taken for laboratory tests. RESULTS: We found that severe pelvic injury was produced with an AIS CV value of 10.32%, and the rabbits demonstrated severe physiologic impairment and coagulo-fibrinolytic derangements with high mortality. In rabbits of group D, however, physiologic and coagulo-fibrinolytic parameters were significantly enhanced with improved organ function and lowered mortality when compared with the other three groups. CONCLUSIONS: We herein established in rabbits a blast- and fragment-induced pelvic injury animal model that exhibited high reproducibility, and we demonstrated that hemostatic resuscitation plus DCS was effective in improving the outcome.

Hemostatic Effects of Bio-Zeolite Gauze and QuikClot Combat Gauze on Major Bleeding in Rabbits Acutely Exposed to High Altitude.

Objective: Hemostatic gauze application is an effective way to control major bleeding, which is the most common cause of death in trauma in both civilian and military settings. Coagulation derangement after acute exposure to high altitude might alter the effects of hemostatic gauzes. The present study aimed to observe the hemostatic effects of bio-zeolite gauze (BZG) and QuikClot Combat Gauze® (QCG) on major bleeding in rabbits acutely exposed to high altitude.Methods: Sixty rabbits were randomly and evenly divided into six groups. Animal models of simulated blast- and fragment-induced inguinal major bleeding were prepared in lower altitude and high-altitude areas, and BZG, QCG, and ordinary gauze without hemostatic material were used to control bleeding. The primary outcomes included immediate hemostasis rate, blood loss, and survival rate, while the secondary outcomes included hemodynamic parameters, laboratory examinations, and coagulation-relevant markers.Results: The overall effects of BZG and QCG were better than those of ordinary gauze, with a higher immediate hemostatic rate, less blood loss, and higher survival rate at 90 min after gauze application and higher red blood cell and platelet counts and lower creatinine level at 30 min after gauze application in lower altitude. The concentrations of coagulation factor XII and factor X in rabbits acutely exposed to high altitude were significantly lower than those in lower altitude. At high altitude, the hemostatic effects of BZG did not decrease significantly compared to those in the lower altitude, whereas those of ordinary gauze and QCG decreased significantly at high altitude compared to those in the lower altitude.Conclusions: Coagulation derangement after acute exposure to high altitude has negative effects on ordinary gauze and QCG but has no significant negative hemostatic effects on BZG.

Animal model-based simulation training for three emergent and urgent operations of penetrating thoracic injuries.

PURPOSE: To develop animal models of penetrating thoracic injuries and to observe the effects of the animal model-based training on improving the trainees' performance for emergent and urgent thoracic surgeries. METHODS: With a homemade machine, animal models of lung injuries and penetrating heart injuries were produced in porcine and used for training of chest tube drainage, urgent sternotomy, and emergent thoracotomy. Coefficient of variation of abbreviated injury scale and blood loss was calculated to judge the reproducibility of animal models. Five operation teams from basic-level hospitals (group A) and five operation teams from level III hospitals (group B) were included to be trained and tested. Testing standards for the operations were established after thorough literature review, and expert questionnaires were employed to evaluate the scientificity and feasibility of the testing standards. Tests were carried out after the training. Pre- and post-training performances were compared. Post-training survey using 7-point Likert scale was taken to evaluate the feelings of the trainees to these training approaches. RESULTS: Animal models of the three kinds of penetrating chest injuries were successfully established and the coefficient of variation of abbreviated injury scale and blood loss were all less than 25%. After literature review, testing standards were established, and expert questionnaire results showed that the scientific score was 7.30 ± 1.49, and the feasibility score was 7.50 ± 0.89. Post-training performance was significantly higher in both group A and group B than pre-training performance. Post-training survey showed that all the trainees felt confident in applying the operations and were generally agreed that the training procedure were very helpful in improving operation skills for thoracic penetrating injury. CONCLUSIONS: Animal model-based simulation training established in the current study could improve the trainees' performance for emergent and urgent thoracic surgeries, especially of the surgical teams from basic-level hospitals.

Establishment of a combat damage control surgery training platform for explosive combined thoraco-abdominal injuries.

PURPOSE: It is challenging to prepare military surgeons with the skills of combat damage control surgery (CDCS). The current study aimed to establish a damage control surgery (DCS) training platform for explosive combined thoraco-abdominal injuries. METHODS: The training platform established in this study consisted of 3 main components: (1) A 50 m × 50 m square yard was constructed as the explosion site. Safety was assessed through cameras. (2) Sixteen pigs were injured by an explosion of trinitrotoluene attached with steel balls and were randomly divided into the DCS group (accepted DCS) and the control group (have not accepted DCS). The mortality rate was observed. (3) The literature was reviewed to identify the key factors for assessing CDCS, and testing standards for CDCS were then established. Expert questionnaires were employed to evaluate the scientificity and feasibility of the testing standards. Then, a 5-day training course with incorporated tests was used to test the efficacy of the established platform. In total, 30 teams attended the first training course. The scores that the trainees received before and after the training were compared. SPSS 11.0 was employed to analyze the results. RESULTS: The high-speed video playback confirmed the safety of the explosion site as no explosion fragments projected beyond the wall. No pig died within 24 h when DCS was performed, while 7 pigs died in the control group. After a literature review, assessment criteria for CDCS were established that had a total score of 100 points and had 4 major parts: leadership and team cooperation, resuscitation, surgical procedure, and final outcome. Expert questionnaire results showed that the scientific score was 8.6 ± 1.25, and the feasibility score was 8.74 ± 1.19. When compared with the basic level, the trainees' score improved significantly after training. CONCLUSION: The platform established in this study was useful for CDCS training.

BND-VGG-19: A deep learning algorithm for COVID-19 identification utilizing X-ray images.

During the past two years, a highly infectious virus known as COVID-19 has been damaging and harming the health of people all over the world. Simultaneously, the number of patients is rising in various countries, with many new cases appearing daily, posing a significant challenge to hospital medical staff. It is necessary to improve the efficiency of virus detection. To this end, we combine modern technology and visual assistance to detect COVID-19. Based on the above facts, for accurate and rapid identification of infected persons, the BND-VGG-19 method was proposed. This method is based on VGG-19 and further incorporates batch normalization and dropout layers between the layers to improve network accuracy. Then, the COVID-19 dataset including viral pneumonia, COVID-19, and normal X-ray images, are used to diagnose lung abnormalities and test the performance of the proposed algorithm. The experimental results show the superiority of BND-VGG-19 with a 95.48% accuracy rate compared with existing COVID-19 diagnostic methods.

Preactivation of ß-catenin in osteoblasts improves the osteoanabolic effect of PTH in type 1 diabetic mice.

Type 1 diabetes (T1D) is correlated with osteopenia primarily due to low bone formation. Parathyroid hormone (PTH) is a known anabolic agent for bone, the anabolic effects of which are partially mediated through the Wnt/ß-catenin signaling pathway. In the present study, we first determined the utility of intermittent PTH treatment in a streptozotocin-induced T1D mouse model. It was shown that the PTH-induced anabolic effects on bone mass and bone formation were attenuated in T1D mice compared with nondiabetic mice. Further, PTH treatment failed to activate ß-catenin signaling in osteoblasts of T1D mice and was unable to improve osteoblast proliferation and differentiation. Next, the Col1-3.2 kb-CreERTM; ß-cateninfx(ex3) mice were used to conditionally activate ß-catenin in osteoblasts by injecting tamoxifen, and we addressed whether or not preactivation of ß-catenin boosted the anabolic action of PTH on T1D-related bone loss. The results demonstrated that pretreatment with activation of osteoblastic ß-catenin followed by PTH treatment outperformed PTH or ß-catenin activation monotherapy and led to greatly improved bone structure, bone mass, and bone strength in this preclinical model of T1DM. Further analysis demonstrated that osteoblast proliferation and differentiation, as well as osteoprogenitors in the marrow, were all improved in the combination treatment group. These findings indicated a clear advantage of developing ß-catenin as a target to improve the efficacy of PTH in the treatment of T1D-related osteopenia.

The increase in bone resorption in early-stage type I diabetic mice is induced by RANKL secreted by increased bone marrow adipocytes.

Bone marrow adipose tissue (BMAT) has recently been found to induce osteoclastogenesis by secreting RANKL. Although Type 1 diabetes mellitus (T1DM) has been reported to be associated with increased BMAT and bone loss, little is known about the relationship between BMAT and osteoclasts in T1DM. We studied the role of BMAT in the alterations of osteoclast activities in early-stage T1DM, by using a streptozotocin-induced T1DM mouse model. Our results showed that osteoclast activity was enhanced in the long bones of T1DM mice, accompanied by increased protein expression of RANKL. However, RANKL mRNA levels in bone tissues of T1DM mice remained unchanged. Meanwhile, we found that BMAT was significantly increased in the long bones of T1DM mice, and both mRNA and protein levels of RANKL were elevated in the diabetic BMAT. More importantly, RANKL protein was mainly expressed on the cell membranes of the increased adipocytes, most of which were located next to the metaphyseal region. These results suggest that the enhanced bone resorption in early-stage diabetic mice is induced by RANKL derived from BMAT rather than the bone tissue itself.

Different effects of Wnt/ß-catenin activation and PTH activation in adult and aged male mice metaphyseal fracture healing.

BACKGROUND: Fractures in older men are not uncommon and need to be healed as soon as possible to avoid related complications. Anti-osteoporotic drugs targeting Wnt/ß-catenin and PTH (parathyroid hormone) to promote fracture healing have become an important direction in recent years. The study is to observe whether there is a difference in adult and aged situations by activating two signal paths. METHODS: A single cortical hole with a diameter of 0.6 mm was made in the femoral metaphysis of Catnblox(ex3) mice and wild-type mice. The fracture healing effects of CA (Wnt/ß-catenin activation) and PTH (activated by PTH (1-34) injections) were assessed by X-ray and CT imaging on days 7, 14, and 21 after fracture. The mRNA levels of ß-catenin, PTH1R(Parathyroid hormone 1 receptor), and RUNX2(Runt-related transcription factor 2) in the fracture defect area were detected using RT-PCR. Angiogenesis and osteoblasts were observed by immunohistochemistry and osteoclasts were observed by TRAP (Tartrate-resistant Acid Phosphatase). RESULT: Adult CA mice and adult PTH mice showed slightly better fracture healing than adult wild-type (WT) mice, but there was no statistical difference. Aged CA mice showed better promotion of angiogenesis and osteoblasts and better fracture healing than aged PTH mice. CONCLUSION: The application of Wnt/ß-catenin signaling pathway drugs for fracture healing in elderly patients may bring better early effects than PTH signaling pathway drugs, but the long-term effects need to be observed.

Different effects of Wnt/ß-catenin activation and parathyroid hormone on diaphyseal and metaphyseal in the early phase of femur bone healing of mice.

Parathyroid hormone (PTH) and agents related to the manipulation of Wnt/ß-catenin signalling are two promising anabolic anti-osteoporotic therapies that have been shown to promote the healing of bone fractures. Now, it is widely accepted that cortical bone and trabecular bone are two different compartments, and should be treated as separate compartments in pathological processes, such as fracture healing. It is currently unknown whether PTH and the activation of ß-catenin signalling would demonstrate different effects on cortical bone and trabecular bone healing. In the current study, single 0.6-mm cortex holes were made in the femur metaphysis and diaphysis of mice, and then, PTH application and ß-catenin activation were used to observe the promoting effect on bone healing. The effects of ß-catenin and PTH signalling on fracture healing were observed by X-ray and CT at 3, 6, and 14 days after fracture, and the levels of ß-catenin were detected by RT-PCR assay, and the number of specific antigen-positive cells of BRDU, OCN, RUNX2 was counted by immunohistochemical staining. While ß-catenin activation and PTH were found to demonstrate similar effects on accelerating metaphyseal bone healing, activation of ß-catenin showed a more striking effect than PTH on promoting diaphyseal bone healing. These findings might be helpful for selecting proper medication to accelerate fracture healing of different bone compartments.

Disruption of bone morphogenetic protein type IA receptor in osteoblasts impairs bone quality and bone strength in mice.

In recent years, several studies have found that the disruption of type IA receptor of bone morphogenetic proteins (BMPR1A) could increase bone mass. However, whether disruption of BMPR1A could have an effect on bone quality and bone strength is currently unknown. Osteoblast-targeted conditional knockout (cKO) of BMPRIA by crossing 3.2-kb Col1-CreER™ mice with BMPR1A fx +/+ mice was conducted. Then, in vitro and in vivo studies were employed to examine the effect of BMPR1A knockout on bone quality and bone strength. It was found that the ultimate force and stiffness of the femora decreased significantly in cKO mice when compared to control mice. The content of collagen and mineralization level decreased as the structure of the collagen became disorganized. The morphology of osteocytes in cKO mice was abnormal as well. The expression level of osteocalcin, a marker for the terminal differentiation of osteoblasts, decreased in cKO mice. This data indicated that the differentiation of osteoblasts in cKO mice was impaired. Immunohistochemistry examination revealed deregulated expression of dickkopf 1(DKK1) in osteocytes in cKO mice. Adding DKK1 to the culture medium reversed these effects. In conclusion, even though disruption of BMPR1A could increase bone mass, it also impairs bone quality and bone strength.

Constitutive ß-catenin activation in osteoblasts impairs terminal osteoblast differentiation and bone quality.

Accumulating evidence suggests that Wnt/ß-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of ß-catenin (CA-ß-catenin) in osteoblasts potentially has side effects on the bone growth and bone remodeling process, although it could increase bone mass. The present study aimed to observe the effects of osteoblastic CA-ß-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-ß-catenin mice exhibited lower mineralization levels and disorganized collagen in long bones as confirmed by von Kossa staining and sirius red staining, respectively. Also, bone strength decreased significantly in CA-ß-catenin mice. Then the effect of CA-ß-catenin on biological functions of osteoblasts were investigated and it was found that the expression levels of osteocalcin, a marker for the late differentiation of osteoblasts, decreased in CA-ß-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-ß-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-ß-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin D1, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-ß-catenin mice, and the expression levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate cells entering into S and G2/M phases, increased in osteoblasts that were isolated from the CA-ß-catenin mice. In summary, osteoblastic CA-ß-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength.

Diagnosis and treatment of rare complications of pelvic fractures.

PURPOSE: To enhance the awareness of rare complications of pelvic fracture and describe the correct diagnosis and effective treatment. METHODS: A total of 188 cases of pelvic fractures were retrospectively reviewed, and four patients who suffered from four types of rare pelvic fracture complications were described, namely ureteral obstruction caused by retroperitoneal hematoma-induced abdominal compartment syndrome (ACS), bowel entrapment, external iliac artery injury, and open scrotal sac injury. RESULTS: We demonstrated that combined measures should be employed to prevent the occurrence of ACS following major pelvic fractures. Ureteral catheter support may be a good option at an early stage when ACS occurred. Contrasted computed tomography examination and sufficient awareness are keys to a correct diagnosis of bowel entrapment following pelvic fractures. Recognition of risk factors, early diagnosis, and prompt treatment of suspected injury of the external iliac artery are keys to patient survival and to avoid limb loss. Scrotal and/or testicular injury complicated by pelvic fractures should be carefully treated to maintain normal gonad function. Additionally, establishment of a sophisticated trauma care system and multi-disciplinary coordination are important for correct diagnosis and treat- ment of rare complications in pelvic fractures. CONCLUSIONS: Rare complications of pelvic fractures are difficult to diagnose and negatively impact outcome. Recognition of risk factors and sufficient awareness are essential for correct diagnosis and prompt treatment.

Percutaneous compression plate versus proximal femoral nail anti-rotation in treating elderly patients with intertrochanteric fractures: a prospective randomized study.

BACKGROUND: The treatment and management of hip fracture poses a great challenge for clinicians in osteology and surgery. The aim of this study is to compare the clinical effectiveness of the percutaneous compression plate (PCCP) versus proximal femoral nail anti-rotation (PFNA) in the treatment of intertrochanteric fractures in elderly patients. METHODS: A prospective randomized study was carried out from January 2008 to October 2011 involving 90 elderly patients with intertrochanteric fractures (90 hips) who underwent minimally invasive surgery using the PCCP or PFNA. Evaluation variables, including operation time, intra- and perioperative blood loss, duration of hospital stay, incidence of postoperative complications, and final clinical outcomes by the end of follow-up, were used to compare the benefits of these two implants. RESULTS: Among 90 subjects, 45 received PCCPs and 45 received PFNAs. The baseline characteristics of the two groups were comparable. The median follow-up time was 16.9 months (12-24 months). In the PCCP group, the mean operative time was 53 min (40-75 min), and the mean intra- and perioperative blood losses were 100.7 ml (60-150 ml) and 916 ml (433-1339 ml), respectively, which were significantly lower than those in the PFNA group. Nevertheless, there was no statistical difference in the incidence of postoperative complications and final clinical outcomes including pain complaints, range of motion of the hip, postoperative hip function at 12 months, and the recovery of walking ability to pre-injury status between these two implants. CONCLUSIONS: Overall, the PCCP and PFNA appear to have similar clinical effects in treating elderly patients with intertrochanteric fractures, although the PCCP provided shorter operation times and less blood loss than PFNA. Both implants discussed were demonstrated to be ideal for the treatment of femoral intertrochanteric fractures in elderly patients.

Features of Coagulo-Fibrinolytic Derangement Due to Bleeding in Nonacclimatized Rabbits Acutely Exposed to High Altitude.

Zhong, Xin, Wenqiong Du, Zhaowen Zong, Renqing Jiang, Yijun Jia, Zhao Ye, and Haoyang Yang. Features of coagulo-fibrinolytic derangement due to bleeding in nonacclimatized rabbits acutely exposed to high altitude. High Alt Med Biol. 24:68-75, 2023. Background: The present study aimed to observe the time course of coagulo-fibrinolytic derangement due to bleeding in rabbits acutely exposed to high altitude (HA). Materials and Methods: Forty-eight rabbits were randomly divided into four groups and were subjected to minor bleeding at low altitude, major bleeding at low altitude, minor bleeding after acute exposure to HA, and major bleeding after acute exposure to HA. To produce minor and major bleeding, 10% and 30% of the total blood volume was removed, respectively. At designated time points, samples were taken for laboratory examination. Results: While minor bleeding at low altitude led to minor coagulo-fibrinolytic derangements, it led to complicated derangements at HA, which presented as an early hypercoagulable state and transition to hypocoagulable and hyperfibrinolytic states with lower clot firmness. Major bleeding at HA resulted in greater derangements of the R time, K values, the D-dimer concentration, the alpha angle, maximum amplitude, and the concentration of fibrinogen than were observed at low altitude. Conclusions: The extent of coagulo-fibrinolytic derangements due to bleeding in rabbits after acute exposure to HA was more severe and complicated than that at low altitude. Therefore, proper resuscitation should be applied based on these changes.

Modified Glucose-insulin-potassium Therapy for Hemorrhage-induced Traumatic Cardiac Arrest in Rabbits.

OBJECTIVE: Resuscitation with whole blood is known to be better than that with saline in attaining the return of spontaneous circulation (ROSC) and improving the short-term survival rate for hemorrhage-induced traumatic cardiac arrest (HiTCA). However, the resuscitation with whole blood alone fails to address the pathophysiological abnormalities, including hyperglycemia, hyperkalemia and coagulopathy, after HiTCA. The present study aimed to determine whether the modified glucose-insulin-potassium (GIK) therapy can ameliorate the above-mentioned pathophysiological abnormalities, enhance the ROSC, improve the function of key organs, and reduce the mortality after HiTCA. METHODS: HiTCA was induced in rabbits (n=36) by controlled hemorrhage. Following arrest, the rabbits were randomly divided into three groups (n=12 each): group A (no resuscitation), group B (resuscitation with whole blood), and group C (resuscitation with whole blood plus GIK). The GIK therapy was administered based on the actual concentration of glucose and potassium. The ROSC rate and survival rate were obtained. Hemodynamical and biochemical changes were detected. Thromboelastography (TEG) was used to measure coagulation parameters, and enzyme-linked immunosorbent assay to detect parameters related to inflammation, coagulation and the function of brain. RESULTS: All animals in groups B and C attained ROSC. Two rabbits died 24-48 h after HiTCA in group B, while no rabbits died in group C. The GIK therapy significantly reduced the levels of blood glucose, potassium, and biological markers for inflammatory reaction, and improved the heart, kidney, liver and brain function in group C when compared to group B. Furthermore, the R values of TEG were significantly lower in group C than in group B, and the maximum amplitude of TEG was slightly lower in group B than in group C, with no significant difference found. CONCLUSION: Resuscitation with whole blood and modified GIK therapy combined can ameliorate the pathophysiological disorders, including hyperglycemia, hyperkalemia and coagulopathy, and may improve the function of key organs after HiTCA.

Electric fields guide migration of epidermal stem cells and promote skin wound healing.

Migration of epidermal stem cells (EpSCs) into wounds may play an important role in wound healing. Endogenous electric fields (EFs) arise naturally at wounds. Consistent with previous reports, we measured outward electric currents at rat skin wounds using vibrating probes. Topical use of prostaglandin E2 significantly promoted wound healing. However, it is not known whether EpSCs respond to EFs. We first isolated and characterized EpSCs from rat skin. We then demonstrated that EpSCs isolated from the epidermis migrated directionally toward the cathode in EFs of 50-400 mV/mm. The directedness values increased in a dose- and time-dependent fashion. The migration speed of EpSCs was significantly increased in EFs. EFs induced asymmetric polymerization of intracellular F-actin and activation of the extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3-kinase (PI3K)/protein kinase B pathways. Inhibition of epidermal growth factor receptor, extracellular signal-regulated kinase 1/2, or PI3K significantly inhibited the cathodal distribution of F-actin and the electrotactic response of EpSCs. These data for the first time show that EpSCs possess obvious electrotaxis, in which the epidermal growth factor receptor-mitogen activated protein kinase-PI3K pathways are involved. These data thus suggest a novel aspect of electric signaling in wound healing-to stimulate and guide migration of EpSCs and to regulate wound healing.

A Novel Scenario-Based, Mixed-Reality Platform for Training Nontechnical Skills of Battlefield First Aid: Prospective Interventional Study.

BACKGROUND: Although battlefield first aid (BFA) training shares many common features with civilian training, such as the need to address technical skills and nontechnical skills (NTSs), it is more highly scenario-dependent. Studies into extended reality show clear benefits in medical training; however, the training effects of extended reality on NTSs, including teamwork and decision-making in BFA, have not been fully proven. OBJECTIVE: The current study aimed to create and test a scenario-based, mixed-reality platform suitable for training NTSs in BFA. METHODS: First, using next-generation modeling technology and an animation synchronization system, a 10-person offensive battle drill was established. Decision-making training software addressing basic principles of tactical combat casualty care was constructed and integrated into the scenarios with Unreal Engine 4 (Epic Games). Large-space teamwork and virtual interaction systems that made sense in the proposed platform were developed. Unreal Engine 4 and software engineering technology were used to combine modules to establish a mixed-reality BFA training platform. A total of 20 Grade 4 medical students were recruited to accept BFA training with the platform. Pretraining and posttraining tests were carried out in 2 forms to evaluate the training effectiveness: one was knowledge acquisition regarding the NTS and the other was a real-world, scenario-based test. In addition, the students were asked to rate their agreement with a series of survey items on a 5-point Likert scale. RESULTS: A battlefield geographic environment, tactical scenarios, scenario-based decision software, large-space teamwork, and virtual interaction system modules were successfully developed and combined to establish the mixed-reality training platform for BFA. The posttraining score of the students' knowledge acquisition was significantly higher than that of pretraining (t=-12.114; P≤.001). Furthermore, the NTS score and the total score that the students obtained in the real-world test were significantly higher than those before training (t=-17.756 and t=-21.354, respectively; P≤.001). However, there was no significant difference between the scores of technical skills that the students obtained before and after training. A posttraining survey revealed that the students found the platform helpful in improving NTSs for BFA, and they were confident in applying BFA skills after training. However, most trainees thought that the platform was not helpful for improving the technical skills of BFA, and 45% (9/20) of the trainees were not satisfied with the simulation effect. CONCLUSIONS: A scenario-based, mixed-reality platform was constructed in this study. In this platform, interaction of the movement of multiple players in a large space and the interaction of decision-making by the trainees between the real world and the virtual world were accomplished. The platform could improve the NTSs of BFA. Future works, including improvement of the simulation effects and development of a training platform that could effectively improve both the technical skills and NTSs of BFA, will be carried out.

Method for Teaching Life-Saving Combat First-Aid Skills With live-actor Patients Using a Wearable Training Apparatus.

INTRODUCTION: Training combat personnel in combat first-aid skills has faced many challenges over time, such as the need to combine tactics with medicine and to overcome combat personnel's lack of medical background knowledge. Therefore, many simulation methods are currently being developed, each of which has its advantages and disadvantages. In this study, a combined simulation method involving live-actor patients using a wearable training apparatus was developed, and the effects of this method were observed. MATERIALS AND METHODS: Focusing on the major causes of preventable deaths among victims killed in action, wearable training apparatuses simulating massive hemorrhage, airway obstruction, and tension pneumothorax were designed and produced. Methods of simulating these three injury types using live-actor patients with these training apparatuses were developed, and medical teachers evaluated the simulation effects. The live-actor patients were incorporated into a tactical scenario to train and test nonmedical and medical students in year 3, respectively. High-fidelity simulator-based training and traditional training without simulation served as the control. A post-training survey using a 7-point Likert scale evaluated the trainees' feelings toward these training approaches. RESULTS: Three types of training apparatuses were developed to simulate three life-threatening injuries, and the simulation effects of the live-actor patients using these apparatuses were highly recognized by medical teachers. Both live-actor patients and high-fidelity simulator-based training improved performance significantly more than traditional training. However, the improvement due to training with live-actor patients was greater than that due to high-fidelity simulator-based training for nonmedical students, whereas there was no difference between these two simulation methods for medical students. A post-training survey revealed that all the trainees were confident in practicing first-aid skills after training, and they all agreed that live-actor patients could combine tactical situations with first aid better than high-fidelity simulators. The nonmedical students strongly agreed that live-actor patients were more helpful in the training of injury evaluation than high-fidelity simulators. CONCLUSIONS: The method using wearable training apparatus-based live-actor patients was satisfying and effective for teaching life-saving combat first-aid skills, especially for nonmedical students.

Time Course of Coagulo-Fibrinolytic Derangements During Acclimatization to High Altitude in Rabbits and a Preliminary Study on the Possible Mechanisms.

Zhong, Xin, Zhao Ye, Xiaolin Zhou, Renqing Jiang, Yijun Jia, Wenqiong Du, Haoyang Yang, Lin Zhang, Bai Lu, and Zhaowen Zong. Time course of coagulo-fibrinolytic derangements during acclimatization to high altitude in rabbits and a preliminary study on the possible mechanisms. High Alt Med Biol. 23:240-248, 2022. Background: Conflicting data exist regarding changes in the coagulation system during acclimatization to high altitude (HA), which makes the prevention of thromboembolic events difficult. The present study aimed at observing the dynamic changes in the coagulo-fibrinolysis system during acclimatization to HA and at exploring the possible mechanisms. Materials and Methods: Twenty rabbits of both sexes were randomly divided into two groups, including group A rabbits (healthy plain controls) and group B rabbits (acutely exposed to HA). A traditional coagulation test, thromboelastography analysis, and full blood cell count were used to assess the coagulo-fibrinolytic changes at different time points. Plasma was collected to examine the levels of relevant biomarkers. Results: Six hours and 1 day after acute exposure to HA, the coagulo-fibrinolytic system demonstrated a hypercoagulable state. Further, 3 days after exposure to HA, group B rabbits showed hypocoagulability, increased fibrinolysis, and lower clot firmness and 7 days after exposure to HA, delayed coagulation, decreased fibrinolysis, and increased clot firmness were observed. Subsequently, 14, 21, and 28 days after exposure to HA, we found increased clot firmness. Increased platelet counts and concentrations of fibrinogen and plasminogen activator inhibitor-1 contributed to this change. Conclusion: The coagulo-fibrinolytic derangements during acclimatization to HA in rabbits demonstrated a dynamic pattern.

Wnt/ß-catenin signalling promotes more effective fracture healing in aged mice than in adult mice by inducing angiogenesis and cell differentiation.

To investigate whether activating the Wnt/ß-catenin signalling pathway differentially promotes fracture healing in aged and adult individuals. CatnbTM2Kem, Catnblox(ex3) and wild-type adult and aged mice were used in this study. The femur was electroporated through a hole with a diameter of 0.6 mm. On the 7th, 14th and 21st days after fracture establishment, repair of the femoral diaphyseal bone was examined using X-ray and CT, the levels of mRNAs related to Wnt/ß-catenin signalling were detected using real-time polymerase chain reaction (RT-PCR), and angiogenesis and cell differentiation were observed using immunohistochemistry. The numbers of osteoclasts were determined by TRAP staining. Wnt/ß-catenin activation accelerated fracture healing in adult mice, with more pronounced effects on aged mice. Compared with wild-type mice at the corresponding ages, Wnt/ß-catenin signalling activation induced higher levels of angiogenesis and cell differentiation in aged mice than in adult mice and promoted fracture healing. The administration of medications targeting Wnt/ß-catenin signalling to aged patients may accelerate fracture healing to a greater extent.