Targeting ONECUT3 blocks glycolytic metabolism and potentiates anti-PD-1 therapy in pancreatic cancer.

BACKGROUND: Reprogramming glucose metabolism, also known as the Warburg effect (aerobic glycolysis), is a hallmark of cancers. Increased tumor glycolysis not only favors rapid cancer cell proliferation but reprograms the immune microenvironment to enable tumor progression. The transcriptional factor ONECUT3 plays key roles in the development of the liver and pancreas, however, limited is known about its oncogenic roles, particularly metabolic reprogramming. METHODS: Immunohistochemistry and Western blotting are applied to determine the expression pattern of ONECUT3 and its clinical relevance in pancreatic ductal adenocarcinoma (PDAC). Knockdown and overexpression strategies are employed to determine the in vitro and in vivo functions of ONECUT3. Chromatin immunoprecipitation, luciferase reporter assay, and gene set enrichment analysis are used to decipher the molecular mechanisms. RESULTS: The glycolytic metabolism is inversely associated with T-cell infiltration in PDAC. ONECUT3 is identified as a key regulator for PDAC glycolysis and CD8+ T-cell infiltration. Genetic silencing of ONECUT3 inhibits cell proliferation, promotes cell apoptosis, and reduces glycolytic metabolism as evidenced by glucose uptake, lactate production, and extracellular acidification rate. Opposite effects of ONECUT3 are observed in overexpression studies. ONECUT3 enhances aerobic glycolysis via transcriptional regulation of PDK1. Targeting ONECUT3 effectively suppresses tumor growth, increases CD8+ T-cell infiltration, and potentiates anti-PD-1 therapy in PDAC. Pharmacological inhibition of PDK1 also shows a synergistic effect with anti-PD-1 therapy. In clinical setting, ONECUT3 is closely associated with PDK1 expression and T-cell infiltration in PDAC and acts as an independent prognostic factor. CONCLUSIONS: Our study reveals a previous unprecedented regulatory role of ONECUT3 in PDAC glycolysis and provides in vivo evidence that increased glycolysis is linked to an immunosuppressive microenvironment. Moreover, targeting ONECUT3-PDK1 axis may serve as a promising therapeutic approach for the treatment of PDAC.

Evaluation of bone mineral density in adolescent idiopathic scoliosis using a three-dimensional finite element model: a retrospective study.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is often accompanied by osteopenia and osteoporosis, which can cause serious complications. The aim of this study was to determine the specific bone mineral density (BMD) of each vertebral body in patients with AIS using biomechanical finite element modeling based on three-dimensional (3D) reconstruction. METHODS: This retrospective study involved 56 patients with AIS. Computed tomography (CT) and radiography were performed. Spinal vertebrae were segmented from the spinal CT images of patients with AIS to reconstruct 3D vertebral models. The vertebral models were meshed into tetrahedral finite elements to assess the BMD. RESULTS: The mean main curve Cobb angle was 88.6 ± 36.7°, and the mean kyphosis angle was 36.8 ± 31.5°. The mean BMD of the global spine was 0.83 ± 0.15 g/cm2. The highest BMD was measured on the concave side of the apex (0.98 ± 0.16 g/cm2). Apical vertebral BMD was negatively correlated with age and height (r = - 0.490, p = 0.009 and r = - 0.478, p = 0.043, respectively). There were no significant differences in BMD values between the concave and convex sides (p > 0.05). CONCLUSIONS: The 3D finite element modeling of BMD in patients with AIS is a reliable and accurate BMD measurement method. Using this method, the overall BMD of patients with AIS was shown to gradually decrease from the top to the bottom of the spine. Our findings provide valuable insights for surgical planning, choice of screw trajectories, and additional biomechanical analyzes using finite element models in the context of scoliosis.

Composite Interventions on Outcomes of Severely and Critically Ill Patients with COVID-19 in Shanghai, China.

Background: The sixty-day effects of initial composite interventions for the treatment of severely and critically ill patients with COVID-19 are not fully assessed. Methods: Using a Bayesian piecewise exponential model, we analyzed the 60-day mortality, health-related quality of life (HRQoL), and disability in 1082 severely and critically ill patients with COVID-19 between 8 December 2022 and 9 February 2023 in Shanghai, China. The final 60-day follow-up was completed on 10 April 2023. Results: Among 1082 patients (mean age, 78.0 years, 421 [38.9%] women), 139 patients (12.9%) died within 60 days. Azvudine had a 99.8% probability of improving 2-month survival (adjusted HR, 0.44 [95% credible interval, 0.24-0.79]), and Paxlovid had a 91.9% probability of improving 2-month survival (adjusted HR, 0.71 [95% credible interval, 0.44-1.14]) compared with the control. IL-6 receptor antagonist, baricitinib and a-thymosin each had a high probability of benefit (99.5%, 99.4%, and 97.5%, respectively) compared to their controls, while the probability of trail-defined statistical futility (HR > 0.83) was high for therapeutic anticoagulation (99.8%; HR, 1.64 [95% CrI, 1.06-2.50]) and glucocorticoid (91.4%; HR, 1.20 [95% CrI, 0.71-2.16]). Paxlovid, Azvudine, and therapeutic anticoagulation showed a significant reduction in disability (p < 0.05) Conclusions: Among severely and critically ill patients with COVID-19 who received 1 or more therapeutic interventions, treatment with Azvudine had a high probability of improved 60-day mortality compared with the control, indicating its potential in a resource-limited scenario. Treatment with an IL-6 receptor antagonist, baricitinib, and a-thymosin also had high probabilities of benefit in improving 2-month survival, among which a-thymosin could improve HRQoL. Treatment with Paxlovid, Azvudine, and therapeutic anticoagulation could significantly reduce disability at day 60.

Secoisolariciresinol diglucoside Ameliorates Osteoarthritis via Nuclear factor-erythroid 2-related factor-2/ nuclear factor kappa B Pathway: In vitro and in vivo experiments.

Osteoarthritis (OA) is an age-related joint disease in which inflammation and extracellular matrix (ECM) degradation play a crucial role in the destruction of articular cartilage. Secoisolariciresinol diglucoside (SDG), the main lignan in wholegrain flaxseed, which has been reported to remarkably suppress inflammation and oxidative stress, may have potential therapeutic value in OA. In this study, the effect and mechanism of SDG against cartilage degeneration were verified in the destabilization of the medial meniscus (DMM) and collagen-induced (CIA) arthritis models and interleukin-1ß (IL-1ß)-stimulated osteoarthritis chondrocyte models. From our experiments, SDG treatment downregulated the expression of pro-inflammatory factors induced by IL-1ß in vitro, including inducible nitric oxide synthase (INOS), cyclooxygenase-2 (COX2), tumor necrosis factor (TNF-α), and interleukin 6 (IL-6). Additionally, SDG promoted the expression of collagen II (COL2A1) and SRY-related high-mobility-group-box gene 9(SOX9), while suppressing the expression of a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5) and matrix metalloproteinases 13(MMP13), which leads to catabolism. Consistently, in vivo, SDG has been identified to have chondroprotective effects in DMM-induced and collagen-induced arthritis models. Mechanistically, SDG exerted its anti-inflammation and anti-ECM degradation effects by activating the Nrf2/HO-1 pathway and inhibiting the nuclear factor kappa B (NF-κB) pathway. In conclusion, SDG ameliorates the progression of OA via the Nrf2/NF-κB pathway, which indicates that SDG may have therapeutic potential for OA.

Retrospective analysis of drug resistance characteristics and infection related risk factors of multidrug-resistant organisms (MDROs) isolated from the orthopedics department of a tertiary hospital.

Patients infected with multidrug-resistant organisms (MDROs) are known to exhibit longer hospital stays and a significantly poorer prognosis. We performed a 6-year retrospective analysis of nosocomial infections reported in the orthopedics department of our institution, to gain valuable insights into antibiotic sensitivity and infectious characteristics of MDROs, in order to deduce effective measures to control the occurrence of multidrug-resistant infections in clinical practice. A retrospective, single center surveillance study (January 2012-December 2017) was performed on the nosocomial infections recorded in the department of orthopedics. A nosocomial infection is defined as one that develops when a patient is residing in a hospital but was not present at the time of admission. All relevant data, including basic patient information, cultivated bacterial strains, and antimicrobial resistance, was obtained from the hospital information system. A total of 1392 strains of pathogenic bacteria were isolated; 358 belonged to MDROs (detection rate = 25.7%). All the isolated strains of MDROs were mostly from secretions (52.2%). The number of cases infected with MDROs were 144 (40.2%) and 129 (36.0%) in the trauma and spinal wards, respectively. MRSA showed high resistance to ß lactam antibiotics, but was sensitive to quinolone antibiotics, linezolid and cotrimoxazole. ESBL-positive strains showed more sensitivity to carbapenem antibiotics (resistance rate < 10%). MDR nonfermenters showed high resistance to most antibiotics. Logistic multivariate analysis revealed age, open injury, and central nervous system injury as independent risk factors for multidrug resistant infections. A high antibiotic resistance rate and an increasing prevalence of infections with MDROs was identified in the orthopedics department. Patients with open injury, central nervous system injury and those aged ≥ 60 years, were more prone to multidrug-resistant infections. Clinicians should pay more attention to such patients in order to actively prevent and control the occurrence of infections caused by MDROs.

Overexpression of hsa_circ_0006470 inhibits the malignant behavior of gastric cancer cells via regulation of miR-1234/TP53I11 axis.

Gastric cancer (GC) is a subtype of a common malignant tumor found in the digestive system. Hsa_circ_0006470 is known to be closely associated with the development of GC. Nevertheless, the mechanism by which hsa_circ_0006470 regulates the tumorigenesis of GC has not been fully elucidated. To investigate the role of hsa_circ_0006470 in GC, its expression levels were assessed in GES-1, AGS, MKN45, and SNU5 cells by reverse transcription-quantitative PCR. Fluorescence in situ hybridization was used to evaluate the localization of hsa_circ_0006470 in AGS and MKN45 cells. In addition, cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were performed to evaluate the viability and proliferation of GC cells, respectively. The dual-luciferase reporter assay was used to explore the interaction among hsa_circ_0006470, microRNA (miR)-1234, and TP53I11. The expression levels of TP53I11, Akt, p-Akt, forkhead box O1, and cyclin dependent kinase 2 in AGS cells were analyzed by Western blotting. The data indicated that hsa_circ_0006470 expression was downregulated in AGS cells. In addition, overexpression (OE) of hsa_circ_0006470 could inhibit the viability and proliferation of GC cells. Moreover, OE of hsa_circ_0006470 inhibited the migration of GC cells and induced G1 cell cycle phase arrest. Moreover, miR-1234 was bound to hsa_circ_0006470 and TP53I11 was targeted by miR-1234. Furthermore, OE of hsa_circ_0006470 inhibited the tumorigenesis of GC via the regulation of the miR-1234/TP53I11 axis. In summary, the present study demonstrated that OE of hsa_circ_0006470 notably inhibited the tumorigenesis of GC by regulating the miR-1234/TP53I11 axis. Therefore, the present study may provide a theoretical basis for exploring novel therapeutic strategies for the treatment of GC.

Epidemiologic Correlation and Drug Resistance Analysis of Pathogenic Bacteria in Different Open Limb Injury External Conditions.

OBJECTIVE: To study the epidemiological correlation and drug resistance of external factors of infection caused by open injury of limbs to pathogens. METHODS: This experiment is a retrospective study. We took the geographical location and climate of Nanchang, Jiangxi Province, China as the background, analyzed 2017 strains of pathogens from 1589 patients with limb trauma infection in a University Affiliated Hospital from 2012 to 2017. Patients were divided into three groups according to the type of incision: I, In-hospital infection of clean limb incision, II, In-hospital infection with open injury, III, Community infection with open injury of the limb. Groups II and Groups III were divided into six subgroups according to the causes of trauma, including: accidents from non-motor vehicles, machinery, cutting/piercing, pedestrian injuries, struck by/against, pedal cycles, and other injuries. We found eight common pathogens of orthopedic infection, which were mainly divided into Gram-positive bacteria (G+, mainly including Staphylococcus) and Gram-negative bacteria (G-, mainly Enterobacteriaceae). The relationship between main pathogens and damage mechanism, apparent temperature and relative humidity was discussed in this study. SPSS v22.0 was used for statistical analysis of the data. Friedman's two-way ANOVA was used to analyze the difference between the injury mechanism and incidence of pathogenic bacteria. Linear regression was used to determine the trend between the incidence of major pathogens and seasonal temperature and humidity. The level of significance was set as P < 0.05. RESULTS: There was no significant difference in the distribution of pathogens between Groups II and Groups III (P>0.05). The drug resistance of Groups III was significantly higher than that of Groups II and Groups I. G+ bacteria were resistant to cephalosporin, ceftriaxone and other cephalosporins and erythromycin and other macrolides. They were sensitive to vancomycin and linezolid. G- were resistant to the first- and the second-generation cephalosporins, including cefotetan and cefazolin, and ampicillin and other penicillins, while they were sensitive to third-generation cephalosporins, such as ceftazidime, as well as to levofloxacin and other quinolones, meropenem, and other beta-lactamases. The correlation between the injury mechanism and infection of pathogenic bacteria was not significant. The monthly average apparent temperature and relative humidity were correlated with the infection rate of pathogenic bacteria. CONCLUSION: In open injury of extremities, apparent temperature and relative humidity is an important risk factor for infection by pathogenic bacteria and the drug resistance of pathogenic bacteria in out-of-hospital infection was lower than that of hospital infection.

Fuzzy Adaptive Switching Control for Stochastic Systems With Finite-Time Prescribed Performance.

The issue of fuzzy adaptive switching control for stochastic systems with arbitrary switching signal and finite-time prescribed performance is investigated in this article. A piecewise function is adopted to characterize finite-time prescribed performance, and the error signal is converted to a new state variable via the tangent function. Unknown functions are approximated via fuzzy-logic systems (FLSs). Based on the stochastic stability theory and common Lyapunov function, a fuzzy adaptive switching control scheme is presented. The control law is proposed for the stochastic switched closed-loop system so that not only all the signals are ensured to be semiglobally uniformly ultimately bounded (SGUUB) in probability but also a residual error related to the finite-time prescribed performance bound is guaranteed. Eventually, simulation studies for a practical system are given to show the effectiveness of the presented fuzzy adaptive switching control scheme.

Investigation of in vivo three-dimensional changes of the spinal canal after corrective surgeries of the idiopathic scoliosis.

OBJECTIVE: To determine the three-dimensional (3D) changes of the spinal canal length (SCL) after corrective surgeries and their association with the radiographic and clinical outcomes of idiopathic scoliosis patients. The length of the spinal cord has been demonstrated to be strongly correlated with the SCL. Understanding the changes in SCL could help determine the morphologic changes in the spinal cord to prevent spinal cord injury. METHODS: Twenty-seven scoliotic patients' 3D spinal canal were investigated using computed tomography images. The SCL between the upper and lower end vertebrae (U/L-EV) was measured at five locations. The radiographic parameters of each patient and the patient-reported outcomes (PROs) scores were also collected. The correlations of the changes of the SCLs with the other factors were analyzed. RESULTS: The SCL between the U/L-EV changed non-uniformly at different locations. The post-operative SCLs were significantly elongated by 7.5 ± 3.5 mm (6.0 ± 2.5%, P < .001) at the concave side and compressed by -2.6 ± 2.6 mm (-1.9 ± 1.9%, P < .001) at the convex side. The elongations of the SCL at the concave and posterior locations were correlated with the radiographic parameters including the pre-operative main Cobb angles (r = .511, P = .006; r = .613, P = .001) and apical vertebral translation (AVT) (r = .481, P = .011; r = .684, P = .000). No PRO scores were found to correlate with the SCL changes. CONCLUSION: The corrective surgeries elongated the spinal canal mainly at the concave side and compressed at the convex side. The main thoracic Cobb angle, the changes of AVT, and Cobb angles were moderately associated with the changes of the SCLs, but no PRO score was found to associate with the changes of the SCLs. The data could be instrumental for the improvement of corrective surgeries that are aimed to maximize the correction of scoliosis and minimize the negative effect on the spinal cord to prevent neurological complications.

Ligament deformation patterns of the craniocervical junction during head axial rotation tracked by biplane fluoroscopes.

BACKGROUND: Frequently, treatment decisions for craniocervical injuries and instability are based on imaging findings, but in vivo ligament kinematics were poorly understood. This study was to determine in vivo deformation patterns of primary ligaments in the craniocervical junction (i.e., C0-2), including the cruciform ligament, alar ligaments, and accessory ligaments, during dynamic head axial rotation. METHODS: The skulls and cervical spines of eight asymptomatic female subjects were dynamically imaged using a biplane fluoroscopic imaging system, when they performed left and right head axial rotations. Using a 3D-to-2D registration technique, the in vivo positions and orientations of cervical segments were determined. An optimization algorithm was implemented to determine ligament wrapping paths, and the resulting ligament deformations were represented by percent elongations. Using paired t-tests, ligament deformations in the end-range position were compared to those in the neutral position. FINDINGS: No significant differences were observed in segmental motions during left and right head rotations (p > 0.05). In general, slight deformations occurred in each component of the cruciform ligament. For the alar ligaments, the ipsilateral ligament was lengthened from -0.7 ± 13.8% to 16.6 ± 15.7% (p < 0.001*). For the accessory ligaments, the contralateral ligament was lengthened from -2.9 ± 7.5% to 10.1 ± 6.2% (p < 0.001*). INTERPRETATION: This study reveals that there are distinct deformation patterns in craniocervical junction ligaments during dynamic axial head rotation. These ligament deformation data can enhance our understanding of the synergic function of craniocervical junction ligaments, and guide the treatment of craniocervical instability.

Influence of structural and material property uncertainties on biomechanics of intervertebral discs - Implications for disc tissue engineering.

This study investigated how variations of structural and material properties of human intervertebral discs (IVDs) affect the biomechanical responses of the IVDs under simulated physiological loading conditions using a stochastic finite element (SFE) model. An SFE method, which combined an anatomic FE model of human lumbar L3-4 segment and probabilistic analysis of its structural and material properties, was used to generate a dataset of 500 random disc samples with varying structural and material properties. The sensitivity of the biomechanical responses, including intervertebral displacements/rotations, intradiscal pressures (IDP), fiber stresses and matrix strains of annulus fibrosus (AF), were systematically quantified under various physiological loading conditions, including a 500N compression and 7.5Nm moments in the 3 primary rotations. Significant variations of the IDPs, IVD displacements/rotations, and stress/strain distributions were found using the dataset of 500 ramdom disc samples. Under all the loading conditions, the IDPs were positively correlated with the Poisson's ratio of the NP (r = 0.46 to 0.75, p = 0.004-0.001) and negatively with the Young's modulus of the annulus matrix (r = -0.48 to -0.65, p = 0.003-0.001). The primary intervertebral rotations were significantly affected by the Young's modulus of the annulus matrix (r = -0.44 to -0.71, p = 0.001-0.032) and the orientations of the annular fibers (r = -0.45 to -0.69, p = 0.001-0.029). The heterogeneity of structures and material properties of the IVD had distinct effects on the biomechanical performances of the IVD. These data could help improve our understanding of the intrinsic biomechanics of the IVD and provide references for optimal design of tissue engineered discs by controlling structural and material properties of the disc components.

Long non-coding RNA HOTAIR/microRNA-761 sponge regulates PPME1 and further influences cell biological functions in thyroid carcinoma.

BACKGROUND: Most well-differentiated thyroid carcinomas display good therapeutic outcomes, but there are still some patients who are not sensitive to the general treatments lose their treatment opportunities. Thus, it is important to understand the molecular mechanisms that cause thyroid carcinoma, so as to find effective diagnostic and therapeutic targets. AIM OF THE STUDY: To explore the role of homeobox transcript antisense RNA (HOTAIR) in thyroid carcinoma through protein phosphatase methylesterase 1 (PPME1) by sponging microRNA 761 (miR-761). METHODS: The regulation network amongst HOTAIR, miR-761 and PPME1 was predicted by online sources. RT-PCR was conducted to evaluate the expression of HOTAIR and miR-761 in tumor tissues. Clinical data was collected and analyzed by Chi-square test. Cell apoptosis and proliferation was evaluated using three types of cancer cells (HTh-7, CAL-62, BCPAP) after treated with si-HOTAIR and miR-761inhibitor. The binding site among HOTAIR, miR-761 and PPME1 was verified by dual luciferase reporter assay. PPME1 expression was measured after HOTAIR and miR-761 were suppressed by western blot. Survival time was measured in nude mice using log-rank test. RESULTS: HOTAIR was expressed to a significantly greater extent than miR-761 in thyroid tumor tissues (P < .001). miR-761 and PPME1 were negatively correlated (coef = -1.91, P < .001). HOTAIR competitively binds to miR-761 and miR-761 directly targets PPME1. HOTAIR was highly correlated with TNM (χ 2 = 5.797, P = .016), tumor size (χ 2 = 7.955, P = .005) and lymphatic metastasis (χ 2 = 6.0, P = .014). HOTAIR promoted cell proliferation and inhibited cell apoptosis, whereas miR-761 did not. HOTAIR elevated and miR-761 suppressed PPME1 expression. HOTAIR expression appears to affect the survival time in vivo. CONCLUSION: HOTAIR regulated thyroid cancer cells by binding to miR-761 through PPME1.

Prediction of biomechanical responses of human lumbar discs - a stochastic finite element model analysis.

BACKGROUND: Accurate biomechanical investigation of human intervertebral discs (IVDs) is difficult because of their complicated structural and material features. AIM: To investigate probabilistic distributions of the biomechanical responses of the IVD by considering varying nonlinear structural and material properties using a stochastic finite element (FE) model. METHODS: A FE model of a L3-4 disc was reconstructed, including the nucleus pulposus (NP), annular matrix and fibers. A Monte Carlo method was used to randomly generate 500 sets of the nonlinear material properties and fiber orientations of the disc that were implemented into the FE model. The FE model was analyzed under seven loading conditions: a 500 N compressive force, a 7.5Nm moment simulating flexion, extension, left-right lateral bending, and left-right axial rotation, respectively. The distributions of the ranges of motion (ROMs), intradiscal pressures (IDP), fiber stresses and matrix strains of the disc were analyzed. RESULTS: Under the compressive load, the displacement varied between 0.29 mm and 0.76 mm. Under the 7.5Nm moment, the ROMs varied between 3.0° and 6.0° in primary rotations. The IDPs varied within 0.3 MPa under all the loading conditions. The maximal fiber stress (3.22 ± 0.64 MPa) and matrix strain (0.27 ± 0.12%) were observed under the flexion and extension moments, respectively. CONCLUSION: The IVD biomechanics could be dramatically affected by the structural and material parameters used to construct the FE model. The stochastic FE model that includes the probabilistic distributions of the structural and material parameters provides a useful approach to analyze the statistical ranges of the biomechanical responses of the IVDs.

In vivo primary and coupled segmental motions of the healthy female head-neck complex during dynamic head axial rotation.

While previous studies have greatly improved our knowledge on the motion capability of the cervical spine, few reported on the kinematics of the entire head-neck complex (C0-T1) during dynamic activities of the head in the upright posture. This study investigated in vivo kinematics of the entire head-neck complex (C0-T1) of eight female asymptomatic subjects during dynamic left-right head axial rotation using a dual fluoroscopic imaging system and 3D-to-2D registration techniques. During one-sided head rotation (i.e., left or right head rotation), the primary rotation of the overall head-neck complex (C0-T1) reached 55.5 ± 10.8°, the upper cervical spine region (C0-2) had a primary axial rotation of 39.7 ± 9.6° (71.3 ± 8.5% of the overall C0-T1 axial rotation), and the lower cervical spine region (C2-T1) had a primary rotation of 10.0 ± 3.7° (18.6 ± 7.2% of the overall C0-T1 axial rotation). Coupled bending rotations occurred in the upper and lower cervical spine regions in similar magnitude but opposite directions (upper: contralateral bending of 18.2 ± 5.9° versus lower: ipsilateral bending of 21.4 ± 5.1°), resulting in a compensatory cervical lateral curvature that balances the head to rotate horizontally. Furthermore, upper cervical segments (C0-1 or C1-2) provided main mobility in different rotational degrees of freedom needed for head axial rotations. Additionally, we quantitatively described both coupled segmental motions (flexion-extension and lateral bending) by correlation with the overall primary axial rotation of the head-neck complex. This investigation offers comprehensive baseline data regarding primary and coupled motions of craniocervical segments during head axial rotation.

A comparison of monoaxial pedicle screw versus polyaxial pedicle screw in short-segment posterior fixation for the treatment of thoracolumbar fractured vertebra.

BACKGROUND: Posterior pedicle screw fixation had been applied to maintain spinal stability and avoid further nerve damage in thoracolumbar fracture. This study aimed to evaluate the efficacy of short-segment posterior fixation with monoaxial pedicle screws versus polyaxial pedicle screws in treating thoracolumbar fracture. METHODS: A total of 75 patients with thoracolumbar fracture who underwent short-segment posterior fixation with monoaxial pedicle screw (group A) or polyaxial pedicle screw (group B) were retrospectively enrolled. The patient demographic and radiological data were analyzed between the two groups. RESULTS: A total of 63 patients with an average age of 44.7±11.5 years were finally recruited in this study. There were no significant differences in age, gender, fracture level, thoracolumbar injury classification and severity scale (TLISS) score, American Spinal Injury Association (ASIA) score, Arbeitsgemeinschaft für Osteosynthesefragen (AO) classification, and hospital stay between the two groups (P>0.05). At the last follow-up, the prevertebral height ratio and normal-to-injured vertebral height ratio were significantly decreased in group A compared to group B (P=0.027 and P=0.007, respectively). CONCLUSIONS: Short-segment posterior fixation with monoaxial or polyaxial pedicle screw for fractured thoracolumbar vertebra can restore injured vertebral height. Compared with polyaxial pedicle screw, monoaxial pedicle screw endows stronger leverage which is more beneficial for restoring injured vertebral height and recovery of the damaged endplate in thoracolumbar short-segment posterior fixation.

Drug resistance of pathogens causing nosocomial infection in orthopedics from 2012 to 2017: a 6-year retrospective study.

BACKGROUND: Hospital-acquired infections (HAIs) are an emerging global problem that increases in-hospital mortality, length of stay, and cost. We performed a 6-year retrospective study to provide valuable insight into appropriate antibiotic use in HAI cases. We also aimed to understand how hospitals could reduce pathogen drug resistance in a population that overuses antibiotics. METHODS: All data (2012-2017) were obtained from the hospital information warehouse and clinical microbiology laboratory. RESULTS: We isolated 1392 pathogen strains from patients admitted to the orthopedics department during 2012-2017. Escherichia coli (14.7%, 204/1392), Enterobacter cloacae (13.9%, 193/1392), and Staphylococcus aureus (11.3%, 157/1392) were the most common pathogens causing nosocomial infections. The dominant Gram-negative bacterium was E. coli, with high resistance to ampicillin, levofloxacin, cotrimoxazole, gentamicin, and ciprofloxacin, in that order. E. coli was least resistant to amikacin, cefoperazone-sulbactam. The most dominant Gram-positive bacterium was S. aureus, highly resistant to penicillin and ampicillin, but not resistant to fluoroquinolones and cotrimoxazole. Analysis of risk factors related to multidrug-resistant bacteria showed that patients with open fractures (Gustillo III B and IIIC) were significantly more susceptible to methicillin-resistant S. aureus infections (p < 0.05). Additionally, extended-spectrum ß-lactamase-producing E. coli infections occurred significantly more often in patients with degenerative diseases (p < 0.05). Elderly patients tended to be more susceptible to multidrug-resistant bacterial infections, but this outcome was not statistically significant. CONCLUSIONS: Antimicrobial resistance is a serious problem in orthopedics. To effectively control antimicrobial resistance among pathogens, we advocate extensive and dynamic monitoring of MDR bacteria, coupled with careful use of antibiotics.

Erratum: Beclin-1 knockdown decreases proliferation, invasion and migration of Ewing sarcoma SK-ES-1 cells via inhibition of MMP-9.

[This corrects the article DOI: 10.3892/ol.2017.7667.].

Investigation of Alterations in the Lumbar Disc Biomechanics at the Adjacent Segments After Spinal Fusion Using a Combined In Vivo and In Silico Approach.

The development of adjacent segment degeneration (ASD) is a major concern after lumbar spinal fusion surgery, but the causative mechanisms remain unclear. This study used a combined in vivo and in silico method to investigate the changes of anatomical dimensions and biomechanical responses of the adjacent segment (L3-4) after spinal fusion (L4-S1) in five patients under weight-bearing upright standing conditions. The in vivo adjacent disc height changes before and after fusion were measured using a dual fluoroscopic imaging system (DFIS), and the measured in vivo intervertebral positions and orientations were used as displacement boundary conditions of the patient-specific three-dimensional (3D) finite element (FE) disc models to simulate the biomechanical responses of adjacent discs to fusion of the diseased segments. Our data (represented by medians and 95% confidence intervals) showed that a significant decrease by - 0.8 (- 1.2, - 0.4) mm (p < 0.05) in the adjacent disc heights occurred at the posterior region after fusion. The significant increases in disc tissue strains and stresses, 0.32 (0.21, 0.43) mm/mm (p < 0.05) and 1.70 (1.07, 3.60) MPa (p < 0.05), respectively, after fusion were found in the posterolateral portions of the outermost annular lamella. The intradiscal pressure of the adjacent disc was significantly increased by 0.29 (0.13, 0.47) MPa after fusion (p < 0.05). This study demonstrated that fusion could cause alterations in adjacent disc biomechanics, and the combined in vivo and in silico method could be a valuable tool for the quantitative assessment of ASD after fusion.

Value of Ultrasound Combined with Immunohistochemistry Evaluation of Central Lymph Node Metastasis for the Prognosis of Papillary Thyroid Carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is often accompanied by cervical lymph node metastasis (LNM). The accuracy of the preoperative ultrasound diagnosis of central LNM (CLNM) is limited. LNM is a high-risk factor for local recurrence and may affect the prognosis. Factors not directly related to tumor proliferation are used for risk assessment in the tumor-node-metastasis (TNM) staging system for thyroid cancer. The present study aimed to investigate the value of ultrasound and immunohistochemistry in predicting the presence of CLNM and the prognosis of PTC. PATIENTS AND METHODS: The ultrasound and immunohistochemistry features of 303 patients with first-ever PTC and who underwent surgery between 01/2014 to 12/2016 were analyzed, as well as the prognosis of the patients. Univariable and multivariable analyses were carried out to determine the risk factors of CLNM and recurrence. RESULTS: Among 303 patients, 125 (41.3%) were pathologically confirmed with CLNM. Multivariable analysis showed that multifocality, taller-than-wide shape, grade III-IV blood flow, capsular invasion, Ki-67 >10%, p53 ≥5%, T2 or T3 stages were independent risk factors for CLNM. The median follow-up was 56 months. Cox regression analysis showed that age ≥55 years, maximum tumor diameter >20 mm, multifocality, capsular invasion, Ki-67 5-10%, Ki-67 >10%, p53 ≥5%, T3 stage and N1a stage were independent risk factors for PTC recurrence. The Kaplan-Meier showed that recurrence-free survival (RFS) was different according to age (P=0.017), tumor size multifocality, capsular invasion, Ki-67, p53, T stage and N stage (all P<0.001). CONCLUSION: For PTC with rich blood flow, taller-than-wide shape, multifocality, capsular invasion, p53 ≥5%, Ki-67 >10%, T2 or T3 stages prophylactic CLNM dissection might be indicated. Age≥55 years, maximum tumor diameter >20 mm, multifocality, capsular invasion, high Ki-67, p53 ≥5%, T3 and N1a stages affected the clinical outcome.

Epidemiology and Drug Resistance Analysis of Mixed Infection in Orthopedic Surgical Sites.

Background: Infection, including mixed infection, is not uncommon in orthopedic surgical incision. This study aimed to investigate the epidemiology and drug resistance of mixed infections after orthopedic surgical procedures. Methods: We retrospectively analyzed 533 orthopedic surgical site infections (SSIs) in a university hospital from 2012 to 2017. Eighty-six patients (218 strains) with bacterial culture results showing more than one strain were screened to explore their epidemiology and drug resistance. Results: Of 218 bacterial strains, 2-7 bacterial infections were noted in each wound. Most infections were caused by two kinds of bacteria (65.1%). The number of infections decreased with increased number of strains. The combinations of pathogenic micro-organisms were all gram-negative, 55.81%; gram-positive and gram-negative, 30.23%; all gram-positive, 12.79%; and gram-positive and fungi, 1.16%. Their resistance is consistent with the bacterial resistance of 447 cases of single bacterial SSI during the same period. Hospitalization duration was longer (9.8-20.6 d). Conclusion: Our study shows no significant changes in epidemiology and drug resistance caused by mixed infections in the orthopedic surgical site because of coordination and competition among micro-organisms. These bacteria are difficult to control, leading to extended hospitalization. Antibiotic agents should be chosen strictly according to drug sensitivity, and ineffective antibiotic agents must be avoided.