Hypoxia preconditioning of adipose stem cell-derived exosomes loaded in gelatin methacryloyl (GelMA) promote type H angiogenesis and osteoporotic fracture repair.

The challenges posed by delayed atrophic healing and nonunion stand as formidable obstacles in osteoporotic fracture treatment. The processes of type H angiogenesis and osteogenesis emerge as pivotal mechanisms during bone regeneration. Notably, the preconditioning of adipose-derived stem cell (ADSC) exosomes under hypoxic conditions has garnered attention for its potential to augment the secretion and functionality of these exosomes. In the present investigation, we embarked upon a comprehensive elucidation of the underlying mechanisms of hypo-ADSC-Exos within the milieu of osteoporotic bone regeneration. Our findings revealed that hypo-ADSC-Exos harboured a preeminent miRNA, namely, miR-21-5p, which emerged as the principal orchestrator of angiogenic effects. Through in vitro experiments, we demonstrated the capacity of hypo-ADSC-Exos to stimulate the proliferation, migration, and angiogenic potential of human umbilical vein endothelial cells (HUVECs) via the mediation of miR-21-5p. The inhibition of miR-21-5p effectively attenuated the proangiogenic effects mediated by hypo-ADSC-Exos. Mechanistically, our investigation revealed that exosomal miR-21-5p emanating from hypo-ADSCs exerts its regulatory influence by targeting sprouly1 (SPRY1) within HUVECs, thereby facilitating the activation of the PI3K/AKT signalling pathway. Notably, knockdown of SPRY1 in HUVECs was found to potentiate PI3K/AKT activation and, concomitantly, HUVEC proliferation, migration, and angiogenesis. The culminating stage of our study involved a compelling in vivo demonstration wherein GelMA loaded with hypo-ADSC-Exos was validated to substantially enhance local type H angiogenesis and concomitant bone regeneration. This enhancement was unequivocally attributed to the exosomal modulation of SPRY1. In summary, our investigation offers a pioneering perspective on the potential utility of hypo-ADSC-Exos as readily available for osteoporotic fracture treatment.

Mechanisms of the Masquelet technique to promote bone defect repair and its influencing factors.

The Masquelet technique, also known as the induced membrane technique, is a surgical technique for repairing large bone defects based on the use of a membrane generated by a foreign body reaction for bone grafting. This technique is not only simple to perform, with few complications and quick recovery, but also has excellent clinical results. To better understand the mechanisms by which this technique promotes bone defect repair and the factors that require special attention in practice, we examined and summarized the relevant research advances in this technique by searching, reading, and analysing the literature. Literature show that the Masquelet technique may promote the repair of bone defects through the physical septum and molecular barrier, vascular network, enrichment of mesenchymal stem cells, and high expression of bone-related growth factors, and the repair process is affected by the properties of spacers, the timing of bone graft, mechanical environment, intramembrane filling materials, artificial membrane, and pharmaceutical/biological agents/physical stimulation.

Metabolomics provides insights into acceleration of bone healing in fractured patients with traumatic brain injuries.

While clinical surveys have frequently reported that patients with traumatic brain injuries (TBIs) and comorbidities experience faster healing, the underlying mechanisms have been investigated but remain unclear. As a comprehensive comparison and analysis of the metabolic characteristics of these two pathologies have not been undertaken, we developed a rat model of fracture and TBI and collected serum samples for metabolomic analysis using ultra-high performance liquid chromatography-quadrupole time-of-flight MS (UHPLC-Q-TOF/MS). In total, we identified 40 differential metabolites and uncovered related pathways and potential mechanisms, including aminoacyl-transfer RNA biosynthesis; differential amino acids such as leucine, cholylhistidine, aspartyl-lysine; and related lipid metabolism, and discussed their impacts on bone formation in detail. This study highlights that the UHPLC-Q-TOF/MS-based metabolomics approach offers a better understanding of the metabolic links between TBI and accelerated bone recovery.

Application of an arched, Ni-Ti shape-memory connector in repairing distal tibiofibular syndesmosis ligament injury.

OBJECTIVE: To investigate the clinical effect of internal fixation of a Ni-Ti arched shape-memory connector in the treatment of distal tibiofibular syndesmosis ligament injury. METHODS: From January 2013 to January 2016, 108 cases of ankle fracture with distal tibiofibular syndesmosis ligament injury in our hospital were selected, and all of them were fixed with ASCs or screw fixation. The functional evaluation and efficacy evaluation were performed according to the Olerud Molander Ankle Score (Omas) and SF-36. At the same time, follow-ups recorded the incidence of postoperative complications: osteoarthritis, superficial infection, symptomatic hard and soft tissue irritation, early removal and poor reduction of internal fixation, and later loss of reduction. RESULTS: In the ASC(Ni-Ti Arched shape-memory Connector) group, the incidence of symptomatic hardware, soft tissue or superficial infection decreased to 2.77%(from 13.8% or 11.1% in SCREW group). The early removal rate(2.77%) of internal fixation was also lower than that of the screw group. While the incidence of osteoarthritis is 13.8% in SCREW group, the incidence of osteoarthritis in the later follow-up was also as low as 1.38% in ASC group. Loss of fracture reduction due to removal of the fixation device for the distal tibiofibular syndesmosis ligament was not observed in the ASC group. With two postoperative scoring systems (OMAS and SF-36), patients in the ASC group significantly get higher score than that in SCREW group. CONCLUSION: The design of the Ni-Ti arched shape-memory connector can be adapted to the irregular anatomical structure of the malleolus and the ability to continue to contract by body temperature. The use of ASCs in fixation of articular ligaments can preserve a slight range of motion, and the results suggest that ASCs can effectively reduce the incidence of fixation looseness, fracture, infection and other complications.

[Development of Novel Guide Device for Cannulated Screws Implantation in Femoral Neck Fracture Surgery].

Cannulated Screw is a common internal fixation for the treatment of femoral neck fractures. However, the traditional implantation method has disadvantages such as inaccuracy and large radiation exposure. Based on the anatomical characteristics of the femoral neck and geometric principles, we develop a novel guide device for cannulated screws insertion. The cadaver experiment showed that it can improve the accuracy of cannulated screws implantation, reduce puncture attempts and the radiation exposure of doctors and patients.

MicroRNA-139-5p Promotes Functional Recovery and Reduces Pain Hypersensitivity in Mice with Spinal Cord Injury by Targeting Mammalian Sterile 20-like Kinase 1.

Currently, there is no cure for spinal cord injury (SCI), a heavy burden on patients physiology and psychology. We found that microRNA-139-5p (miR-139-5p) expression was significantly downregulated in damaged spinal cords in mice. So, we aimed to test the effect of treatment with miR-139-5p on functional recovery and neuropathic pain in mice with SCI and investigate the underlying mechanism. The luciferase reporter assay revealed that miR-139-5p directly targeted mammalian sterile 20-like kinase 1 (Mst1), and miR-139-5p treatment suppressed Mst1 protein expression in damaged spinal cords of mice. Wild-type mice and Mst1(-/-) mice were exposed to SCI and treated with miR-139-5p agomir via intrathecal infusion. Treatment of SCI mice with miR-139-5p accelerated locomotor functional recovery, reduced hypersensitivities to mechanical and thermal stimulations, and promoted neuronal survival in damaged spinal cords. Treatment with miR-139-5p enhanced phosphorylation of adenosine monophosphate-activated protein kinase alpha (AMPKα), improved mitochondrial function, and suppressed NF-κB-related inflammation in damaged spinal cords. Deficiency of Mst1 had similar benefits in mice with SCI. Furthermore, miR-139-5p treatment did not provide further protection in Mst1(-/-) mice against SCI. In conclusion, miR-139-5p treatment enhanced functional recovery and reduced pain hypersensitivity in mice with SCI, possibly through targeting Mst1.

Iron overload threatens the growth of osteoblast cells via inhibiting the PI3K/AKT/FOXO3a/DUSP14 signaling pathway.

Iron overload is a common stress in the development of cells. Growing evidence has indicated that iron overload is associated with osteoporosis. Therefore, enhancing the understanding of iron overload would benefit the development of novel approaches to the treatment of osteoporosis. The purpose of the present study was to analyze the effect of iron overload on osteoblast cells, via the MC3T3-E1 cell line, and to explore its possible underlying molecular mechanisms. Ferric ammonium citrate (FAC) was utilized to simulate iron overload conditions in vitro. FAC-induced iron overload strongly suppressed proliferation of osteoblast cells and induced apoptosis. Moreover, iron overload strongly suppressed the expression of dual-specificity phosphatase 14 (DUSP14). Additionally, overexpression of DUSP14 protected osteoblast cells from the deleterious effects of iron overload, and this protective effect was mediated by FOXO3a. Additionally, matrine rescued the function of DUSP14 in osteoblast cells. Most importantly, our analysis demonstrated the essential role of the PI3K/AKT/FOXO3a/DUSP14 signaling pathway in the defense against iron overload in osteoblast cells. Overall, our results not only elucidate deleterious effects of iron overload, but also unveil its possible signaling pathway in osteoblast cells.

Novel laser positioning navigation to aid puncture during percutaneous nephrolithotomy: a preliminary report.

PURPOSE: Accurate puncture of the renal collecting system is crucial to the success of percutaneous nephrolithotomy and presents a technical challenge for urologists. Here, we introduced the Surgical Approach Visualization and Navigation (SAVN) system, a novel navigation system to assist puncture and reduce intraoperative radiation. MATERIALS AND METHODS: Twenty kidneys of 10 cadavers were randomly divided into two groups for renal calyx puncture. In the control group, traditional fluoroscopy was used for guidance, while SAVN system was used in the experimental group. Puncture duration, number of puncture attempts, total number of intraoperative fluoroscopies, and number of fluoroscopies during the puncture procedure were recorded. RESULTS: The puncture duration was 14.2 ± 2.5 s in SAVN group and 48.3 ± 7.1 s in conventional group (P < 0.05). One puncture attempt was needed for successful puncture in SAVN group, while more than one in conventional group (P = 0.28). The total number of intraoperative fluoroscopies was 3.3 ± 1.0 in SAVN group and 14.5 ± 3.1 in control group (P < 0.05),while the number of fluoroscopies during the puncture procedure was 0 and 11.2 ± 2.4, respectively (P < 0.05). CONCLUSIONS: The novel SAVN system has a simplified structure and is easy to use. It can be used to successfully assist with puncture of the renal calyx, thus reducing puncture duration and radiation dose.

Treatment of open tibial diaphyseal fractures by external fixation combined with limited internal fixation versus simple external fixation: a retrospective cohort study.

BACKGROUND: The treatment of open tibial shaft fractures is challenging. External fixation (EF) is comparatively safe in treating these open injuries, meanwhile it has the advantages of easy application, minimal additional disruption, and convenient subsequent soft tissue repair. Nevertheless, its application is accompanied by a series of problems in alignment and bone healing. Therefore, limited internal fixation (LIF), such as cortical screws, has been used based on the external fixator for better therapeutic effect. The aim of this study is to compare the outcomes of EF combined with LIF and simple EF in the management of open tibial shaft fractures, evaluating the efficacy and safety of using the combined technique in treating such fractures. METHODS: From January 2012 to December 2016, patients with open tibial shaft fractures treated with EF with or without LIF augmentation were identified. A total of 152 patients were included in the analysis, and there were 85 patients in the simple external fixation group and 67 patients in the EF-LIF group. General assessment indicators included the direct cost of hospitalization and the times of first surgery, full weight bearing, and complete union. Infections and complications in union or limb alignment were compared as primary outcomes. Additionally, the number of patients who changed the fixation system for various reasons were analysed. RESULTS: Effective follow-up of all participants for statistical analysis was obtained. The follow-up time averaged 17.15 months (range: 12.00 to 24.00 months) in the EF group and 16.20 months (range: 12.00 to 19.00 months) in the EF-LIF group. Combined fixation provided shortened time to bear full weight and achieve complete bone union, while requiring additional first surgery time. No significant difference was found in infection rates or direct cost of hospitalization. Delayed union and non-union in the EF-LIF group were significantly decreased (20.9% versus 40.0, 1.5% versus 14.1%, p < 0.05). In limb alignment, patients with combined fixation exhibited reduced malreduction, loss of reduction, and malunion. In terms of secondary fixation, the EF-LIF group showed a markedly lower incidence (5.8% versus 34.1%, p < 0.001). CONCLUSION: Compared with simple EF, combined fixation is an effective and safe alternative for management of open tibial diaphyseal fractures. It provides superior initial reduction, better stability and decreases the risk of inferior alignment and delayed union without increasing the risk of infection.

Assessment of radiation exposure in balloon kyphoplasty using a new navigation system.

Study design: Randomized controlled trials of conventional and laser-navigated technology techniques for balloon kyphoplasty were carried out. Objective: To evaluate the effectiveness of a new laser navigation system in reducing the radiation dose in balloon kyphoplasty procedures. Material and methods: Sixty-seven randomized controlled trials involving a total of 75 lumbar vertebrae were treated. Thirty-four vertebrae were treated by regular fluoroscopic imaging alone, and the other 41 vertebrae were treated using the new laser navigation system. For each procedure the fluoroscopy dosage was documented using a Hitachi-Aloka Medical external dosimeter. The operation time was recorded. Results: The amount of radiation exposure in the control group was 870.59 ± 134.27 µSv. A significant reduction of the fluoroscopy usage in the navigated group was detected (503.5 ± 70.0 µSv (p < .0001)). In the control group, the average procedure time was 51.47 ± 8.30 minutes. The average procedure time in the navigated group was significantly reduced (39.26 ± 5.87 minutes (p < .0001)). Conclusion: The laser positioning and navigation system is an effective solution for reducing radiation exposure in balloon kyphoplasty. The increased technical effort may lead to a significant decrease of procedure time. The clinical trial No.: ChiCTR-INR-17013051.

Deletion of mammalian sterile 20-like kinase 1 attenuates neuronal loss and improves locomotor function in a mouse model of spinal cord trauma.

Neuronal cell death following spinal cord injury (SCI) is an important contributor to neurological deficits. The purpose of our work was to delineate the function of mammalian sterile 20-like kinase 1 (Mst1), a pro-apoptotic kinase and key mediator of apoptotic signaling, in the pathogenesis of an experimental mouse model of SCI. Male mice received a mid-thoracic spinal contusion injury, and it was found that phosphorylation of Mst1 at the injured site was enhanced significantly following SCI. Furthermore, when compared to the wild-type controls, Mst1-deficient mice displayed improved locomotor function by increased Basso mouse scale score. Deletion of Mst1 in mice attenuated loss of motor neurons and suppressed microglial and glial activation following SCI. Deletion of Mst1 in mice reduced apoptosis via suppressing cytochrome c release and caspase-3 activation following SCI. Deletion of Mst1 attenuated mitochondrial dysfunction and increased ATP formation following SCI. Deletion of Mst1 in mice inhibited local inflammation following SCI, evidenced by reduced activities of myeloperoxidase and protein levels of TNF-α, IL-1ß, and IL-6. In conclusion, the present study demonstrated that deletion of Mst1 attenuated neuronal loss and improved locomotor function in a mouse model of SCI, via preserving mitochondrial function, attenuating mitochondria-mediated apoptotic pathway, and suppressing inflammation, at least in part.

Highly Effective Antibacterial Vesicles Based on Peptide-Mimetic Alternating Copolymers for Bone Repair.

It is an important challenge for bone repair to effectively deliver growth factors and at the same time to prevent and cure inflammation without obvious pathogen resistance. We designed a kind of antibacterial peptide-mimetic alternating copolymers (PMACs) to effectively inhibit and kill both Gram-positive and Gram-negative bacteria. The minimum inhibition concentrations (MICs) of the PMACs against E. coli and S. aureus are 8.0 µg/mL, which are much lower than that of antibacterial peptides synthesized by other methods such as widely used ring-opening polymerization of N-carboxyanhydride. Furthermore, the PMACs can self-assemble into polymer vesicles (polymersomes) in pure water with low cytotoxicity (IC50 > 1000 µg/mL), which can encapsulate growth factors in aqueous solution and release them during long-term antibacterial process for facilitating bone repair. We also find that the alternating structure is essential for the excellent antibacterial activity. The in vivo tests in rabbits confirmed that the growth-factor-encapsulated antibacterial vesicles have better bone repair ability compared with control groups without antibacterial vesicles. Overall, we have provided a novel method for designing PMAC-based highly effective intrinsically antibacterial vesicles that may have promising biomedical applications in the future.

[Progress on application of hydrogels in the field of peripheral nerve injury repair].

As one of the common traumatic diseases in clinical practice, peripheral nerve injury (PIN) often causes nerve pain, abnormal reflexes, autonomic disorders, and even sensorimotor disorders due to the slow regeneration rate after injury, which seriously affects body function. Even as the gold standard of treatment, autologous nerve transplantation has limitations such as limited donor area and donor injury, which greatly limits its clinical application effect. Therefore, the preparation of artificial nerve grafts suitable for clinical practice has become the future development trend of peripheral nerve injury treatment, and the repair of injury defects and the promotion of nerve regeneration have also become research hotspots in tissue engineering and regenerative medicine. In recent years, extensive research has been carried out on nerve guidance conduits (NGCs) in the field of nerve regeneration and repair, in which scaffold materials and internal fillers have also become the focus of research as the core elements of neural catheters, and a series of achievements have been made in the application of new materials, embedding stem cells/precursor cells, and developing trophic factors and drug-loaded sustained-release systems. Therefore, this paper focuses on the application progress of hydrogel and its related derivative materials in the field of peripheral nerve injury repair, and provides new ideas for promoting the related research of tissue engineering and clinical medicine.

The prediction of the survival in patients with severe trauma during prehospital care: Analyses based on NTDB database.

PURPOSE: Traumas cause great casualties, accompanied by heavy economic burdens every year. The study aimed to use ML (machine learning) survival algorithms for predicting the 8-and 24-hour survival of severe traumas. METHODS: A retrospective study using data from National Trauma Data Bank (NTDB) was conducted. Four ML survival algorithms including survival tree (ST), random forest for survival (RFS) and gradient boosting machine (GBM), together with a Cox proportional hazard model (Cox), were utilized to develop the survival prediction models. Following this, model performance was determined by the comparison of the C-index, integrated Brier score (IBS) and calibration curves in the test datasets. RESULTS: A total of 191,240 individuals diagnosed with severe trauma between 2015 and 2018 were identified. Glasgow Coma Scale (GCS), trauma type, age, SaO2, respiratory rate (RR), systolic blood pressure (SBP), EMS transport time, EMS on-scene time, pulse, and EMS response time were identified as the main predictors. For predicting the 8-hour survival with the complete cases, the C-indexes in the test sets were 0.853 (0.845, 0.861), 0.823 (0.812, 0.834), 0.871 (0.862, 0.879) and 0.857 (0.849, 0.865) for Cox, ST, RFS and GBM, respectively. Similar results were observed in the 24-hour survival prediction models. The prediction error curves based on IBS also showed a similar pattern for these models. Additionally, a free web-based calculator was developed for potential clinical use. CONCLUSION: The RFS survival algorithms provide non-parametric alternatives to other regression models to be of clinical use for estimating the survival probability of severe trauma patients.

Heat stress induces a three-phase thermoregulatory response in different hot and humid environments in rats.

As global warming intensifies, heat waves occur more frequently around the world. Heat stress from hot and humid environments poses a significant threat to human health. It can cause a significant increase in core body temperature (CBT), and even lead to life-threatening heat stroke. Extremely high CBT is considered the most important clinical symptom and prognostic indicator of heat stroke. To study it, we implanted temperature-monitoring capsules into the abdominal cavities of rats to measure their CBT values. The rats were then exposed to different hot and humid environments to monitor the resultant changes in their CBTs. The results showed that heat stress could induce a three-phase thermoregulatory response in rats under different conditions. A temperature plateau was observed as part of the three-phase thermoregulatory response, at a similar CBT across different conditions. The duration of this plateau can reflect the thermotolerance of rats in hot and humid environments. The third stage of the three-phase thermoregulatory response reflects the pathogenesis of heat stroke, which may present the key stage of heat injury. Moreover, a certain range of humidity did not affect the thermoregulatory responses of rats, but exerted a significant impact once a certain threshold was reached. In this study, the CBTs of the rats in different environments were monitored to characterize their thermoregulatory responses under heat stress. In particular, the discovery of the plateau phase and humidity threshold may help to better understand the effects of high temperature and humidity conditions on living organisms.

Heat acclimation with probiotics-based ORS supplementation alleviates heat stroke-induced multiple organ dysfunction via improving intestinal thermotolerance and modulating gut microbiota in rats.

Heat stroke (HS) is a critical condition with extremely high mortality. Heat acclimation (HA) is widely recognized as the best measure to prevent and protect against HS. Preventive administration of oral rehydration salts III (ORSIII) and probiotics have been reported to sustain intestinal function in cases of HS. This study established a rat model of HA that was treated with probiotics-based ORS (ORSP) during consecutive 21-day HA training. The results showed that HA with ORSP could attenuate HS-induced hyperthermia by regulating thermoregulatory response. We also found that HA with ORSP could significantly alleviate HS-induced multiple organ injuries. The expression levels of a series of heat-shock proteins (HSPs), including HSP90, HSP70, HSP60, and HSP40, were significantly up-regulated from the HA training. The increases in intestinal fatty acid binding protein (I-FABP) and D-Lactate typically seen during HS were decreased through HA. The representative TJ proteins including ZO-1, E-cadherin, and JAM-1 were found to be significantly down-regulated by HS, but sustained following HA. The ultrastructure of TJ was examined by TEM, which confirmed its protective effect on the intestinal barrier protection following HA. We also demonstrated that HA raised the intestinal levels of beneficial bacteria Lactobacillus and lowered those of the harmful bacteria Streptococcus through 16S rRNA gene sequencing. These findings suggest that HA with ORSP was proven to improve intestinal thermotolerance and the levels of protective gut microbiota against HS.

DNAJA1­knockout alleviates heat stroke­induced endothelial barrier disruption via improving thermal tolerance and suppressing the MLCK­MLC signaling pathway.

Endothelial barrier disruption plays a key role in the pathophysiology of heat stroke (HS). Knockout of DNAJA1 (DNAJA1­KO) is thought to be protective against HS based on a genome­wide CRISPR­Cas9 screen experiment. The present study aimed to illustrate the function of DNAJA1­KO against HS in human umbilical vein endothelial cells. DNAJA1­KO cells were infected using a lentivirus to investigate the role of DNAJA1­KO in HS­induced endothelial barrier disruption. It was shown that DNAJA1­KO could ameliorate decreased cell viability and increased cell injury, according to the results of Cell Counting Kit­8 and lactate dehydrogenase assays. Moreover, HS­induced endothelial cell apoptosis was inhibited by DNAJA1­KO, as indicated by Annexin V­FITC/PI staining and cleaved­caspase­3 expression using flow cytometry and western blotting, respectively. Furthermore, the endothelial barrier function, as measured by transepithelial electrical resistance and FITC­Dextran, was sustained during HS. DNAJA1­KO was not found to have a significant effect on the expression and distribution of cell junction proteins under normal conditions without HS. However, DNAJA1­KO could effectively protect the HS­induced decrease in the expression and distribution of cell junction proteins, including zonula occludens­1, claudin­5, junctional adhesion molecule A and occludin. A total of 4,394 proteins were identified using proteomic analysis, of which 102 differentially expressed proteins (DEPs) were activated in HS­induced wild­type cells and inhibited by DNAJA1­KO. DEPs were investigated by enrichment analysis, which demonstrated significant enrichment in the 'calcium signaling pathway' and associations with vascular­barrier regulation. Furthermore, the 'myosin light­chain kinase (MLCK)­MLC signaling pathway' was proven to be activated by HS and inhibited by DNAJA1­KO, as expected. Moreover, DNAJA1­KO mice and a HS mouse model were established to demonstrate the protective effects on endothelial barrier in vivo. In conclusion, the results of the present study suggested that DNAJA1­KO alleviates HS­induced endothelial barrier disruption by improving thermal tolerance and suppressing the MLCK­MLC signaling pathway.

Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy.

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress in vitro. Reactive oxygen species (ROS) production was significantly increased following heat stress, and Yoda1 exacerbated the rise in ROS release. GSK2795039, an inhibitor of NADPH oxidase 2 (NOX2), reversed the Yoda1-mediated aggravation of cellular injury and ROS generation after heat stress. The in vivo experiments demonstrate the well photothermal conversion efficiency of TiCN under the 1,064 nm laser irradiation, and Yoda1 increases the sensitivity of breast tumors to PTT in the presence of TiCN. Our study reveals that Piezo1 activation might serve as a photothermal sensitizer for PTT, which may develop as a promising therapeutic strategy for breast cancer.

Absence of NF-κB subunit p50 ameliorates cold immobilization stress-induced gastric ulcers.

Stress ulcers are a common complication in critically ill patients, but the underlying mechanism is little known. This study characterized the function of the p50 subunit of NF-κB in an experimental model of cold immobilization stress-induced gastric ulcers. Stress-induced gastric mucosal inflammation and gastric injury were examined in wild-type and NF-κB p50-deficient mice. When subjected to cold immobilization stress, NF-κB was rapidly activated in the gastric mucosa in WT mice whereas the majority of κB DNA-binding activity was abrogated from p50(-/-) mice. Deficiency of p50 ameliorated stress-induced expression of TNF-α, MIP-2, and ICAM-1, resulting in reduced mucosal accumulation of neutrophils and gastric injury. These data indicated a critical role for the p50 in the gastric mucosal inflammatory response to cold restraint stress.

Massive heterotopic ossification associated with late deficits in posterior wall of acetabulum after failed acetabular fracture operation.

BACKGROUND: Heterotopic ossification is a common postoperative complication of acetabular fracture. However, functionally significant heterotopic ossification with associated late bone defects in the posterior wall of the acetabulum is rare and challenging to treat. When heterotopic ossification is a late complication of failed acetabular fracture operation, it is disabling and may only be treated by THA. THA is highly susceptible to premature failure in young and active patients and may require numerous revisions. CASE PRESENTATION: This article describes a 40-year-old man with massive heterotopic ossification associated with late bone defects in the posterior wall of the acetabulum after a failed acetabular fracture operation. The primary fracture type was a 62-A2.3 fracture according to the AO/OTA Classification.Surgical excision and anatomical reconstruction of the acetabular wall using heterotopic ossific bone were performed 10 months after the fracture repair. Postoperatively, indomethacin was administered for prophylaxis against recurrence of heterotopic ossification, and hip range of motion was progressively increased. At 5 years and 6 months follow-up, the patient's pain was relieved and hip function had recovered. Though radiography and CT showed minimal subchondral cysts and mild joint-space narrowing, there was no evidence of graft resorption, progressive posttraumatic osteoarthritis or necrosis of the femoral head. CONCLUSION: To the authors' knowledge, this is the first case of such a challenging condition. Although it is an extremely rare case, it provides an attractive option for avoiding THA, as the long-term follow-up shows a satisfactory outcome.