Icariin mitigates anxiety-like behaviors induced by hemorrhagic shock and resuscitation via inhibiting of astrocytic activation.

BACKGROUND: Abnormal activation of astrocytes in the amygdala contributes to anxiety after hemorrhagic shock and resuscitation (HSR). Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)-associated epigenetic reprogramming of astrocytic activation is crucial to anxiety. A bioactive monomer derived from Epimedium icariin (ICA) has been reported to modulate NF-κB signaling and astrocytic activation. PURPOSE: The present study aimed to investigate the effects of ICA on post-HSR anxiety disorders and its potential mechanism of action. METHODS: We first induced HSR in mice through a bleeding and re-transfusion model and selectively inhibited and activated astrocytes in the amygdala using chemogenetics. Then, ICA (40 mg/kg) was administered by oral gavage once daily for 21 days. Behavioral, electrophysiological, and pathological changes were assessed after HSR using the light-dark transition test, elevated plus maze, recording of local field potential (LFP), and immunofluorescence assays. RESULTS: Exposure to HSR reduced the duration of the light chamber and attenuated open-arm entries. Moreover, HSR exposure increased the theta oscillation power in the amygdala and upregulated NF-κB p65, H3K27ac, and H3K4me3 expression. Contrarily, chemogenetic inhibition of astrocytes significantly reversed these changes. Chemogenetic inhibition in astrocytes was simulated by ICA, but chemogenetic activation of astrocytes blocked the neuroprotective effects of ICA. CONCLUSION: ICA mitigated anxiety-like behaviors induced by HSR in mice via inhibiting astrocytic activation, which is possibly associated with NF-κB-induced epigenetic reprogramming.

Bone cement reinforcement improves the therapeutic effects of screws in elderly patients with pelvic fragility factures.

BACKGROUND: Pelvic fragility fractures in elderly individuals present significant challenges in orthopedic and geriatric medicine due to reduced bone density and increased frailty associated with aging. METHODS: This study involved 150 elderly patients with pelvic fragility fractures. The patients were divided into two groups, the observation group (Observation) and the control group (Control), using a random number table. Artificial intelligence, specifically the Tianji Orthopedic Robot, was employed for surgical assistance. The observation group received bone cement reinforcement along with screw fixation using the robotic system, while the control group received conventional screw fixation alone. Follow-up data were collected for one-year post-treatment. RESULTS: The observation group exhibited significantly lower clinical healing time of fractures and reduced bed rest time compared to the control group. Additionally, the observation group experienced less postoperative pain at 1 and 3 months, indicating the benefits of bone cement reinforcement. Moreover, patients in the observation group demonstrated significantly better functional recovery at 1-, 3-, and 6-months post-surgery compared to the control group. CONCLUSION: The combination of bone cement reinforcement and robotic technology resulted in accelerated fracture healing, reduced bed rest time, and improved postoperative pain relief and functional recovery.

TiRobot-Assisted Percutaneous Cannulated Screw Fixation for Elderly Patients with Fragility Fractures of the Pelvis: A Retrospective Study.

OBJECTIVE: The incidence of fragility fractures of the pelvis (FFPs) is increasing in the elderly population, and FFPs that require fixation are a challenge for orthopedic surgeons. The insertion of implants is not risk free due to the complex anatomical and osteoporotic bones and requires a steep learning curve. This study aimed to investigate the clinical efficacy of TiRobot-assisted percutaneous cannulated screw fixation in the treatment of elderly FFP patients. METHOD: The clinical data of 46 elderly FFP patients who had been treated with percutaneous cannulated screw fixation from May 2020 to September 2022 were retrospectively analyzed. Twenty-four patients were treated with percutaneous cannulated screw fixation assisted by the TiRobot (TiRobot-assisted group) and 22 patients were treated with conventional freehand surgery (freehand group). Postoperative outcomes, including Matta value, excellent and good rate (EGR) of fracture reduction, and accuracy of screw placement (ASP), were compared. Changes in the Visual analog scale (VAS) pain score and the Majeed score were recorded and compared between groups before and after surgery and during the 24-week follow-up. Repeated-measures analysis of variance (ANOVA) and effect sizes were used as analysis methods. RESULTS: A total of 90 screws were implanted, 51 screws in the TiRobot-assisted group and 39 screws in the freehand group. The operation time of the two groups was 34.1 ± 2.67 min versus 64.5 ± 4.19 min (p < 0.001). There were no screw-related complications or revision surgeries in any group. The Matta value of the TiRobot-assisted group was 5.13 ± 3.52, which was significantly lower than that of the freehand group (9.00 ± 3.68, p < 0.001), while the EGR was 91.67% versus 72.73%, with statistical significance (p < 0.001). The ASP was 100% in the TiRobot-assisted group, better than that in the freehand group, where it was 85.7% (p = 0.043). At each timepoint in the early postoperative period, the VAS score of the TiRobot-assisted group was significantly lower than that of the freehand group and was close to consistent by the last follow-up; the Majeed score of the former was significantly higher than that of the latter at each timepoint of follow-up, with statistical significance (p < 0.001). CONCLUSION: TiRobot-assisted percutaneous cannulated screw fixation of elderly FFP patients is advantageous over conventional freehand surgery, with less invasion, more accurate screw placement, better fracture reduction, early pain relief, and rapid recovery, suggesting that Freehand method to stabilize FFP in the elderly population.

Hemorrhagic Shock and Resuscitation Causes Excessive Dopaminergic Signaling in the mPFC and Cognitive Dysfunction.

Peri-operative hemorrhagic shock and resuscitation (HSR), a severe traumatic stress, is closely associated with post-operative anxiety, depression, and cognitive dysfunction, subsequently causing a serious burden on families and society. Following the co-release of corticotropin-releasing factor and catecholamine, traumatic stress activates dopaminergic neurons, increasing the addictive behavior and neurocognitive impairment risks. This study investigates the association between cognitive dysfunction and dopaminergic neurons in the mPFC under HSR conditions. This study established an HSR model by bleeding and re-transfusion in the mice. After HSR exposure, a dopamine D1 receptor antagonist, SKF-83566, was administered intraperitoneally for three consecutive days. Novel object recognition (NOR), conditioned fearing (FC), and conditioned place preference (CPP) were used to assess cognitive changes 16 days after HSR exposure. Local field potential (LFP) in the mPFC was also investigated during the novel object exploration. Compared with the mice exposed to sham, there was a significant decrease in the object recognition index, a reduction in context- and tone-related freezing time, an increase in CPP values, a downregulation of ß-power but upregulation of γ-power in the mPFC in the mice exposed to HSR. Moreover, the mice exposed to HSR showed significantly upregulated TH-positive cell number, cleaved caspase-1- and TH-positive cells, and interleukin (IL)-1ß/18 expression in the mPFC compared with sham; SKF-83566 could partially reverse these alternations. The HSR caused excessive dopaminergic signaling and cognitive dysfunction in the mPFC, a condition that might be ameliorated using a dopamine D1 receptor inhibitor.

Galectin-1 promotes angiogenesis and chondrogenesis during antler regeneration.

BACKGROUND: Deer antlers are the only known mammalian structure that undergoes full regeneration. In addition, it is peculiar because when growing, it contains vascularized cartilage. The differentiation of antler stem cells (ASCs) into chondrocytes while inducing endochondral extension of blood vessels is necessary to form antler vascularized cartilage. Therefore, antlers provide an unparalleled opportunity to investigate chondrogenesis, angiogenesis, and regenerative medicine. A study found that Galectin-1 (GAL-1), which can be used as a marker in some tumors, is highly expressed in ASCs. This intrigued us to investigate what role GAL-1 could play in antler regeneration. METHODS: We measured the expression level of GAL-1 in antler tissues and cells by immunohistochemistry, WB and QPCR. We constructed antlerogenic periosteal cells (APCs, one cell type of ASCs) with the GAL-1 gene knocked out (APCGAL-1-/-) using CRISPR-CAS9 gene editing system. The effect of GAL-1 on angiogenesis was determined by stimulating human umbilical vein endothelial cells (HUVECs) using APCGAL-1-/- conditioned medium or adding exogenous deer GAL-1 protein. The effect of APCGAL-1-/- on chondrogenic differentiation was evaluated compared with the APCs under micro-mass culture. The gene expression pattern of APCGAL-1-/- was analyzed by transcriptome sequencing. RESULTS: Immunohistochemistry revealed that GAL-1 was widely expressed in the antlerogenic periosteum (AP), pedicle periosteum (PP) and antler growth center. Western blot and qRT-PCR analysis using deer cell lines further supports this result. The proliferation, migration, and tube formation assays of human umbilical vein endothelial cells (HUVECs) showed that the proangiogenic activity of APCGAL-1-/- medium was significantly decreased (P < 0.05) compared with the APCs medium. The proangiogenic activity of deer GAL-1 protein was further confirmed by adding exogenous deer GAL-1 protein (P < 0.05). The chondrogenic differentiation ability of APCGAL-1-/- was impeded under micro-mass culture. The terms of GO and KEGG enrichment of the differentially expressed genes (DEGs) of APCGAL-1-/- showed that down-regulated expression of pathways associated with deer antler angiogenesis, osteogenesis and stem cell pluripotency, such as the PI3K-AKT signaling pathway, signaling pathways regulating pluripotency of stem cells and TGF-ß signaling pathway. CONCLUSIONS: Deer GAL-1, has strong angiogenic activity, is widely and highly expressed in deer antler. The APCs can induce angiogenesis by secreting GAL-1. The knockout of GAL-1 gene of APCs damaged its ability to induce angiogenesis and differentiate into chondrocytes. This ability is crucial to the formation of deer antler vascularized cartilage. Moreover, Deer antlers offer a unique model to explore explore how angiogenesis at high levels of GAL-1 expression can be elegantly regulated without becoming cancerous.

Serum Irisin is Associated with Bone Mineral Density in Postmenopausal T2dm Patients Complicated with Osteoporosis and in Mice with Diabetic Osteoporosis.

BACKGROUND: Osteoporosis is a systemic bone disease with low bone mass, destruction of bone microstructure, and increased bone fragility. Gender and metabolic status are well-known risk factors for osteoporosis. Irisin is a newly discovered myokine that is secreted by skeletal muscle and adipose tissue. Serum Irisin was reported to be decreased in type 2 diabetes mellitus (T2DM) and/or osteoporosis patients, and it is correlated with bone mineral density (BMD) of neck bone, but its role in postmenopausal T2DM with osteoporosis remains largely unknown. METHODS: Postmenopausal T2DM patients with or without osteoporosis were recruited, and 50 agematched healthy postmenopausal women were employed as healthy control. C57BL/6J mice were intraperitoneally injected with 65 mg/kg Streptozotocin (STZ) daily for consecutive 5 days to induce diabetes, and 1 mg/kg recombinant Irisin protein was injected into diabetic mice through the tail vein once a week for 4 months. RESULTS: Compared to that of healthy control, serum Irisin levels and BMD in L1-L4 lumbar spine, femoral neck, total hip, and Wards were decreased in postmenopausal T2DM patients and further decreased in T2DM patients with osteoporosis. Moreover, serum Irisin levels were also correlated with BMD in the above body parts in T2DM patients. Furthermore, recombinant Irisin protein improved diabetic osteoporosis and inflammation in STZ-induced diabetic mice with osteoporosis. CONCLUSION: Serum Irisin levels in postmenopausal T2DM patients with osteoporosis were significantly decreased, which may be related to the decreased BMD and the occurrence of osteoporosis in postmenopausal T2DM patients. The combined measurement of serum Irisin levels and BMD in patients with T2DM in the early stage has a certain effect on the diagnosis and treatment of osteoporosis.

A novel sternoclavicular hook plate for treatment of proximal clavicle fracture with dislocation of sternoclavicular join.

PURPOSE: The aim of this study was to explore the efficacy of sternoclavicular hook plate for treatment of proximal clavicle fracture with dislocation of sternoclavicular joint. METHODS: Between October 2016 and December 2020, 16 cases (9 male and 7 female patient, with a mean age of (42 ± 10) years) of proximal clavicle fracture with dislocation of sternoclavicular joint were included in the study. Injured side, injury mechanism, time to surgery, Complications and duration of follow-up were recorded. The outcomes were evaluated with radiographic assessment, American Shoulder and Elbow Surgeons' Form (ASES). All the patients were evaluated on postoperative 3rd, 6th, and 12th months. RESULTS: According to the ASES scoring system, the average score was 49 ± 4 (preoperative score), 87 ± 5 (3 months follow-up), 88 ± 3 (6 months follow-up) and 91 ± 3 (12 months follow-up). Statistics differences was showed between preoperative and 3,6,12 months follow-up score of ASES score (p < 0.001). The postoperative physical function was better than the preoperative function. Internal fixation failure and fracture non-union complications in two patients. CONCLUSION: Our study indicates that open reduction and sternoclavicular hook plate fixation for the treatment of traumatic sternoclavicular fracture is a safe, relatively straightforward surgical procedure that can lead to satisfactory outcomes.

Pinocembrin relieves hip fracture-induced pain by repressing spinal substance P signaling in aged rats.

Whether pinocembrin (PCN) could be used to alleviate hip fracture-induced pain is investigated in this research. Aged rats with hip fractures were treated with vehicle or 80 mg/kg/day PCN from week 3 to week 4. Then, hind paw mechanical allodynia, unweighting, warmth, and thickness were measured. The microglia and astrocytes activation and proliferation markers in the spinal dorsal horn were detected with real-time PCR and immunofluorescence staining. The relative expression of substance P and its receptor, tachykinin receptor 1 (Tacr1), was detected with enzyme-linked immunosorbent assay (ELISA) and Western blots. The antinociceptive effect of Tacr1 inhibitor LY303870 was also testified. PCN alleviated hip fracture-induced hind paw nociceptive (allodynia and unweighting) and vascular changes (warmth and thickness) in aged rats with diminished microglia and astrocytes activation and proliferation in the spinal dorsal horn. Upregulated substance P and Tacr1 were induced after hip fracture, which could be reversed by PCN treatment. Furthermore, LY303870 treatment partially reversed both spinal nociceptive sensitization and vascular changes after hip fracture. Substance P signaling contributes to the nociceptive and vascular changes observed in the hip fracture, which could be alleviated by PCN.NEW & NOTEWORTHY Substance P signaling contributes to the nociceptive and vascular changes observed in hip fracture, which could be alleviated by PCN.

Digital analysis of external fixation area of proximal humerus fractures in elderly patients.

INTRODUCTION: The purpose is based on anatomical basis, combined with three-dimensional measurement, to guide the clinical repositioning of proximal humeral fractures, select the appropriate pin entry point and angle, and simulate surgery. METHODS: 11 fresh cadaveric specimens were collected, the distance of the marked points around the shoulder joint was measured anatomically, and the vertical distance between the inferior border of the acromion and the superior border of the axillary nerve, the vertical distance between the apex of the humeral head and the superior border of the axillary nerve, the vertical distance between the inferior border of the acromion and the superior border of the anterior rotator humeral artery, and the vertical distance between the apex of the humeral head and the superior border of the anterior rotator humeral artery were marked on the 3D model based on the anatomical data to find the relative safety zone for pin placement. RESULTS: Contralateral data can be used to guide the repositioning and fixation of that side of the proximal humerus fracture, and uniform data cannot be used between male and female patients. For lateral pining, the distance of the inferior border of the acromion from the axillary nerve (5.90 ± 0.43) cm, range (5.3-6.9) cm, was selected for pining along the medial axis of the humeral head, close to the medial cervical cortex, and the pining angle was measured in the coronal plane (42.84 ± 2.45)°, range (37.02° ~ 46.31°), and in the sagittal plane (28.24 ± 2.25)°, range (19.22° ~ 28.51°). The pin was advanced laterally in front of the same level of the lateral approach point to form a cross-fixed support with the lateral pin, and the pin angle was measured in the coronal plane (36.14 ± 1.75)°, range (30.32° ~ 39.61°), and in the sagittal plane (28.64 ± 1.37)°, range (22.82° ~ 32.11°). Two pins were taken at the greater humeral tuberosity for fixation, with the proximal pin at an angle (159.26 ± 1.98) to the coronal surface of the humeral stem, range (155.79° ~ 165.08°), and the sagittal angle (161.76 ± 2.15)°, with the pin end between the superior surface of the humeral talus and the inferior surface of the humeral talus. The distal needle of the greater humeral tuberosity was parallel to the proximal approach trajectory, and the needle end was on the inferior surface of the humeral talus. CONCLUSION: Based on the anatomical data, we can accurately identify the corresponding bony structures of the proximal humerus and mark the location of the pin on the 3D model for pin placement, which is simple and practical to meet the relevant individual parameters.

Comparison of three methods of Müller type C2 and C3 distal femoral fracture repair.

BACKGROUND: We compared the outcomes of three fixation techniques for Müller type C2 and C3 distal femoral fractures. METHODS: We retrospectively analyzed patients undergoing internal fixation for Müller type C2 and C3 distal femoral fractures via locking plate (Group A), lateral locking condylar plate and medial contoured reconstruction plate (Group B), and lateral locking condylar plate and anterior reconstruction plate (Group C). Knee joint functional recovery and functional outcomes were evaluated 12 months postoperatively. RESULTS: Patients included 34 men and 24 women aged 25 to 74 years (mean, 50.3 ± 10.73 years). Operating times were longest in Group B and similar in Groups A and C. Bleeding volume in Group A was smaller than in Group B and similar to that of Group C. Functional outcomes were excellent in 18 (31%) fractures, good in 24 (41%), moderate in 11 (19%), and poor in 5 (9%). Good-to-excellent results were achieved in 56%, 82%, and 83% of patients (Groups A, B, and C, respectively). Groups B and C's outcomes were superior to Group A's outcomes. No significant difference in postoperative complications between the groups existed. CONCLUSION: Lateral locking condylar and anterior reconstruction plating was useful for complex type C distal femoral fractures.

[Application of self-made fine-tuning device in distal locking process of femoral interlocking intramedullary nail].

OBJECTIVE: To evaluate the curative efficacy of self-made fine-tuning setting in the process of femoral distal implantation of intramedullary nail. METHODS: From October 2015 to October 2017, 66 cases of femoral shaft fracture were treated with anterograde interlocking intramedullary nail including 45 males and 21 females with a mean age of(37.21±11.18) years old. Among them, 36 cases were treated with the manufacture's aiming device and self-made fine-tuning setting (research group), other 30 cases were treated with the manufacture's aiming device(control group). The mean operation time, the times of C-arm scan in surgery, the post-operation complications and the fracture union were observed and compared in two groups. RESULTS: Sixty-two cases acquired 8 to 15 months with a mean time of 12.4 months follow-up visit. The post-operation complications and the fracture union between the two groups had no significant difference(P>0.05), the mean operation time and the times of C-arm scan in surgery had statistically significant difference(P<0.05). CONCLUSIONS: Self-made fine-tuning setting in the process of femoral interblocking intramedullary nail could shorten operation time and reduce the the times of C-arm scan.