MiR-2113 overexpression attenuates sepsis-induced acute pulmonary dysfunction, inflammation and fibrosis by inhibition of HMGB1.

Purpose: Sepsis-induced acute lung injury is related to high mortality. MiR-2113 possesses important functions in human diseases. This research aimed to clarify the role and mechanism of miR-2113 in sepsis-induced acute lung injury. Methods: The expression of miR-2113 in lipopolysaccharide (LPS)-induced MLE-12 cells, serum of sepsis patients, and cecal ligation and puncture mouse models was examined using quantitative real-time PCR. The functions of miR-2113 in LPS-treated MLE-12 cells were estimated by Cell Counting Kit-8 assay, flow cytometry, enzyme-linked immunosorbent assay, Western blot, and immunofluorescence. The influences of miR-2113 in cecal ligation and puncture-induced acute lung injury in mice were assessed by hematoxylin-eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, acute pulmonary dysfunction analysis, lactate dehydrogenase levels and total protein concentrations in bronchoalveolar lavage fluid, and Masson staining. Also, the mechanism of miR-2113 was examined using a dual-luciferase reporter assay. Results: MiR-2113 expression was decreased in LPS-induced MLE-12 cells, serum of sepsis patients, and cecal ligation and puncture mouse models. miR-2113 overexpression restored LPS-reduced MLE-12 cell proliferation, but alleviated LPS-induced apoptosis and markers of inflammation and fibrosis in MLE-12 cells. Moreover, we found that miR-2113 mimic reduced LPS-induced MLE-12 cell injury by negatively regulating high-mobility group box 1. In vivo data further confirmed that miR-2113 overexpression alleviated acute pulmonary dysfunction, inflammation and fibrosis in cecal ligation and puncture-induced sepsis mice. Conclusion: MiR-2113 relieved sepsis-induced acute pulmonary dysfunction, inflammation and fibrosis through decreasing high-mobility group box 1.

Tourniquet use benefits to reduce intraoperative blood loss in patients receiving total knee arthroplasty for osteoarthritis: An updated meta-analysis with trial sequential analysis.

PURPOSE: The efficacy and safety of tourniquets use during total knee arthroplasty (TKA) in patients with osteoarthritis remain debated. This updated systematic review and meta-analysis aimed to further evaluate the role of tourniquets use in patients undergoing TKA for knee osteoarthritis by introducing trial sequential analysis. METHODS: PubMed, Embase, and the Cochrane Library were searched. We used the Cochrane risk of bias tool for quality assessment. Statistical heterogeneity across studies was evaluated using Cochran's Q and I2 statistic. Meta-analysis was performed using Stata/SE 14.0, and trail sequential analysis was performed using TSA software version 0.9.5.10 Beta. In addition, qualitative summary was also used to describe results. RESULTS: 15 randomized controlled trials (RCTs) involving 1202 patients were included in the meta-analysis. The pooled results showed that tourniquet use during TKA significantly reduced intraoperative blood loss (mean difference (MD)= -123.84, 95% confidence interval (CI): -163.37 to -84.32, p < .001)and shortened operation time (MD = -4.71, 95% CI: -7.6 to -1.82, p = .001), but there were no significant differences in postoperative blood loss, calculated blood loss, total blood loss, transfusion rate (p = .939), and deep venous thrombosis (DVT) rate between the tourniquet and no-tourniquet groups. TSA confirmed that the result of operation time was false positive, but the results of other outcomes were conclusive. The results of qualitative summary showed conflicting findings in terms of pain, range of motion (RoM) and swelling ratio between the two groups. CONCLUSIONS: Tourniquet use in patients receiving TKA for osteoarthritis benefits to reduce intraoperative blood loss but has no effect on postoperative blood loss, calculated blood loss, total blood loss, operation time, transfusion rate, and DVT rate. In addition, it remains unclear the difference between the tourniquet and non-tourniquet groups in terms of pain, RoM and swelling ratio.

High Expression of CXCL10/CXCR3 in Ventilator-Induced Lung Injury Caused by High Mechanical Power.

BACKGROUND: The energy delivered by a ventilator to the respiratory system in one minute is defined as mechanical power (MP). However, the effect of ventilator-induced lung injury (VILI) in patients suffering from acute respiratory distress syndrome (ARDS) is still unknown. Our previous studies revealed that CXCL10 may be a potential biomarker of lung injury in ARDS. Therefore, the aim of this study was to compare the lung injury of rats and patients under different MP conditions to explore the involvement of CXCL10 and its receptor CXCR3 in VILI. METHODS: Patients were divided into the high mechanical power group (HMPp group) and low mechanical power group (LMPp group), while rats were assigned to the high mechanical power group (HMPr group), medium mechanical power group (MMPr group), and low mechanical power group (LMPr group). CXCL10 and CXCR3 plasma content in ARDS patients and rats under ventilation at different MP was measured, as well as their protein and mRNA expression in rat lungs. RESULTS: CXCL10 and CXCR3 content in the plasma of ARDS patients in the HMPp was significantly higher than that in the LMPp. The increase of MP during mechanical ventilation in the rats gradually increased lung damage, and CXCL10 and CXCR3 levels in rat plasma gradually increased with the increase of MP. CXCL10 and CXCR3 protein and mRNA expression in the HMPr group and MMPr group was significantly higher than that in the LMPr group (P < 0.05). More mast cells were present in the trachea, bronchus, blood vessels, and lymphatic system in the rat lungs of the HMPr group, and the number of mast cells in the HMPr group (13.32 ± 3.27) was significantly higher than that in the LMPr group (3.25 ± 0.29) (P < 0.05). CONCLUSION: The higher the MP, the more severe the lung injury, and the higher the CXCL10/CXCR3 expression. Therefore, CXCL10/CXCR3 might participate in VILI by mediating mast cell chemotaxis.

Acute reduction of erector spinae muscle cross-sectional area is associated with ICU-AW and worse prognosis in patients with mechanical ventilation in the ICU: A prospective observational study.

BACKGROUND: To investigate the values of erector spinae muscle cross-sectional area (ESMcsa) loss for diagnosing intensive care unit-acquired weakness (ICU-AW) and predicting the 60-day survival status in patients with mechanical ventilation. METHODS: Patients who were admitted into the intensive care unit (ICU) and received invasive mechanical ventilation therapy from June 2018 to June 2020 were selected. And they were divided into an ICU-AW group and a non-ICU-AW group, which were compared based on the ESMcsa and The British Medical Research Council muscle strength score (MRC-score) on the 1st and 7th day of ICU admission. The receiver operating characteristic curve was employed to measure the values of the ESMcsa Loss and ESMcsa Loss Ratio on the 7th day in order to diagnose ICU-AW in patients with mechanical ventilation. The survival curves of the patients were plotted to analyze the ESMcsa Loss Ratio values for predicting the 60-day survival status. RESULTS: A total of 104 patients were enrolled, they were divided into the ICU-AW group (n = 56) and the non-ICU-AW group (n = 48). The mechanical ventilation time, ICU stay time, and hospital stay time of the ICU-AW group were all significantly higher than those of the non-ICU-AW group. On the 1st day, no significant difference in the ESMcsa or MRC-score between the 2 groups of patients was observed. On the 7th day, the ESMcsa and MRC-score of the ICU-AW group were significantly lower than those of the non-ICU-AW group. The ESMcsa Loss and ESMcsa Loss Ratio were both significantly negatively correlated with the MRC-score. The ESMcsa Loss and ESMcsa Loss Ratio on the 7th day were both valuable for the prediction of ICU-AW in patients with mechanical ventilation (areas under the receiver operating characteristic curve = 0.904, 0.835, and 0.889, P < .001). The survival rate of the patients in the high- and low-ESMcsa Loss Ratio groups were 60.0% and 80.0% (P < .05). CONCLUSIONS: As suggested by the ESMcsa Loss Ratios of the patients with mechanical ventilation on the 7th day of ICU admission, it offers a desirable objective indicator for the diagnosis of ICU-AW, and provides certain values for predicting the 60-day survival status of patients with mechanical ventilation in the ICU.

Correlation Analysis between Mechanical Power and Lung Ultrasound Score and Their Evaluation of Severity and Prognosis in ARDS Patients.

METHODS: A total of 121 patients with moderate to severe ARDS admitted to the intensive care unit (ICU) from June 2017 to April 2020 and treated with invasive mechanical ventilation were sequentially included in this study. Their general information was collected, and MP was recorded at 0 h, 24 h, 48 h, and 72 h after admission to the ICU. Professionally trained researchers performed the LUS assessments. Patients were divided into the death and survival groups according to their 28-day prognosis. The trend of MP and LUS at the four time points was analyzed. A receiver operating characteristic curve (ROC) was used to analyze the predictive value of MP and LUS scores at 0 h and 72 h for the prognosis (28-day mortality rate) of patients with moderate to severe ARDS. RESULTS: 121 patients were included in the analysis, of which 73 were male and 48 were female. When patients entered the ICU, their oxygenation index (t: 30885, P < 0.01), APACHE II score (t: 2.105, P < 0.05), and SOFA score (t: 4.134, P < 0.001) were higher in the death group than the survival group. The death group had significantly higher MP and LUS at each time point (0 h, 24 h, 48 h, and 72 h) compared to the survival group (all P < 0.05). There was a significant upward trend over time in the MP and LUS of the death group, contrasting to a significant downward trend in the survival group (all P < 0.05). The Pearson correlation analysis showed that MP and LUS were significantly positively correlated at each time point (r values: 0 h: 0.3027; 24 h: 0.3705; 48 h: 0.3902; 72 h: 0.5916; all P < 0.01). The ROC curves showed that MP and LUS at 72 h were of significant value in predicting the prognosis of ARDS patients, with areas under the curve of 0.866 ± 0.032 and 0.839 ± 0.037, respectively. CONCLUSION: There was a significant correlation between the MP and LUS of ARDS patients at four time points from 0 to 72 h, which has a clinical value in evaluating severity and prognosis.

An optimization method for implantation parameters of individualized TKA tibial prosthesis based on finite element analysis and orthogonal experimental design.

BACKGROUND: Individualized and accurate implantation of a tibial prosthesis during total knee arthroplasty (TKA) can assist in uniformly distributing the load and reducing the polyethylene wear to obtain a long-term prosthetic survival rate, but individualized and accurate implantation of a tibial prosthesis during TKA remains challenging. The purpose of this study was to optimize and individualize the positioning parameters of a tibial prosthesis to improve its accurate implantation using a new method of finite element analysis in combination with orthogonal experimental design. METHODS: Ten finite element models of TKA knee joint were developed to optimize the implantation parameters (varus angle, posterior slope angle, and external rotation angle) of tibial prosthesis to reduce the peak value of the contact pressure on the polyethylene liner according to the method of finite element analysis in combination with orthogonal experimental design. The influence of implantation parameters on the peak value of the contact pressure on the polyethylene liner was evaluated based on a range analysis in orthogonal experimental design. RESULTS: The optimal implantation parameters for tibial prosthesis included 0° varus, 1° posterior slope, and 4° external rotation. Under these conditions, the peak value of the contact pressure on the polyethylene liner remained the smallest (16.37 MPa). Among the three parameters that affect the peak value of the contact pressure, the varus angle had the greatest effect (range = 6.70), followed by the posterior slope angle (range = 2.36), and the external rotation angle (range = 2.15). CONCLUSIONS: The optimization method based on finite element analysis and orthogonal experimental design can guide the accurate implantation of the tibial prosthesis, reducing the peak value of the contact pressure on the polyethylene liner. This method provides new insights into the TKA preoperative plan and biomechanical decision-making for accurately implanting TKA prosthesis.

Optimization of parameters for femoral component implantation during TKA using finite element analysis and orthogonal array testing.

BACKGROUND: Individualized and accurate implantation of a femoral component during total knee arthroplasty (TKA) is essential in achieving equal distribution of intra-articular stress and long-term survival of the prosthesis. However, individualized component implantation remains challenging. This study aimed to optimize and individualize the positioning parameters of a femoral component in order to facilitate its accurate implantation. METHODS: Using computer-simulated TKA, the positioning parameters of a femoral component were optimized individually by finite element analysis in combination with orthogonal array testing. Flexion angle, valgus angle, and external rotation angle were optimized in order to reduce the peak value of the pressure on the polyethylene liner of the prosthesis. RESULTS: The optimal implantation parameters of the femoral component were as follows: 1° flexion, 5° valgus angle, and 4° external rotation. Under these conditions, the peak value of the pressure on the polyethylene liner surface was minimized to 16.46 MPa. Among the three parameters, the external rotation angle had the greatest effect on the pressure, followed by the valgus angle and the flexion angle. CONCLUSION: Finite element analysis in combination with orthogonal array testing can optimize the implantation parameters of a femoral component for TKA. This approach would possibly reduce the wear of the polyethylene liner and prolong the survival of the TKA prosthesis, due to its capacity to minimize stress. This technique represents a new method for preoperative optimization of the implantation parameters that can achieve the best possible TKA outcome.

Bioinformatic analysis of Msx1 and Msx2 involved in craniofacial development.

Msx1 and Msx2 were revealed to be candidate genes for some craniofacial deformities, such as cleft lip with/without cleft palate (CL/P) and craniosynostosis. Many other genes were demonstrated to have a cross-talk with MSX genes in causing these defects. However, there is no systematic evaluation for these MSX gene-related factors. In this study, we performed systematic bioinformatic analysis for MSX genes by combining using GeneDecks, DAVID, and STRING database, and the results showed that there were numerous genes related to MSX genes, such as Irf6, TP63, Dlx2, Dlx5, Pax3, Pax9, Bmp4, Tgf-beta2, and Tgf-beta3 that have been demonstrated to be involved in CL/P, and Fgfr2, Fgfr1, Fgfr3, and Twist1 that were involved in craniosynostosis. Many of these genes could be enriched into different gene groups involved in different signaling ways, different craniofacial deformities, and different biological process. These findings could make us analyze the function of MSX gens in a gene network. In addition, our findings showed that Sumo, a novel gene whose polymorphisms were demonstrated to be associated with nonsyndromic CL/P by genome-wide association study, has protein-protein interaction with MSX1, which may offer us an alternative method to perform bioinformatic analysis for genes found by genome-wide association study and can make us predict the disrupted protein function due to the mutation in a gene DNA sequence. These findings may guide us to perform further functional studies in the future.

Three-dimensional reconstruction of subject-specific knee joint using computed tomography and magnetic resonance imaging image data fusions.

Three-dimensional reconstruction of human body from a living subject can be considered as the first step toward promoting virtual human project as a tool in clinical applications. This study proposes a detailed protocol for building subject-specific three-dimensional model of knee joint from a living subject. The computed tomography and magnetic resonance imaging image data of knee joint were used to reconstruct knee structures, including bones, skin, muscles, cartilages, menisci, and ligaments. They were fused to assemble the complete three-dimensional knee joint. The procedure was repeated three times with respect to three different methods of reference landmarks. The accuracy of image fusion in accordance with different landmarks was evaluated and compared with each other. The complete three-dimensional knee joint, which included 21 knee structures, was accurately developed. The choice of external or anatomical landmarks was not crucial to improve image fusion accuracy for three-dimensional reconstruction. Further work needs to be done to explore the value of the reconstructed three-dimensional knee joint for its biomechanics and kinematics.

The effect of overexpression of Dlx2 on the migration, proliferation and osteogenic differentiation of cranial neural crest stem cells.

Craniofacial skeleton mainly originate from the cranial neural crest stem cells (CNCCs), which is a subpopulation of neural crest stem cells (NCCs). Dlx2, a member of the homeodomain family of transcription factors, plays crucial roles in the development of the CNCCs derived craniofacial skeleton. Previous reports reveal that Dlx2-targeted null mutation resulted in anomalies in the skeletal derivatives of CNCCs in mice. Dlx2 overexpression in ova disturbed the migration and differentiation of affected CNCCs and induced the development of ectopic skeleton elements. However, whether Dlx2 overexpression can impair the morphogenesis of CNCCs derived craniofacial skeleton in vivo has not been explored. Here, we generated a transgenic mouse overexpressing Dlx2 in NCCs (Wnt1Cre::iZEG-Dlx2). The Wnt1Cre::iZEG-Dlx2 embryos showed decreased cell proliferation, increased cell apoptosis, abnormal chondrogenesis and impaired osteogenesis within the CNCCs population, resulting in obvious craniofacial defects that ranged from a cleft lip and midfacial clefts to neural tube defects and exencephaly. Adult Wnt1Cre::iZEG-Dlx2 mice showed nasal and premaxillary hypoplasia and spinal deformities. These findings reveal that Dlx2 overexpression in NCCs may be a new pathogenesis of facial cleft and spinal kyphosis in mammals, and may offer us a useful model organism to find suitable therapy methods for these genetic defects that may be different from the traumatic defect and resected defect.