Chinese Medicine Supplementing Qi and Activating Blood Circulation Relieves the Progression of Diabetic Cardiomyopathy.

BACKGROUND: Diabetic cardiomyopathy (DCM) is the leading cause of diabetic death as the final occurrence of heart failure and arrhythmia. Traditional Chinese medicine is usually used to treat various diseases including diabetes. OBJECTIVE: This study sought to investigate the effects of Traditional Chinese medicine supplementing Qi and activating blood circulation (SAC) in DCM. METHODS: After the construction of the DCM model by streptozotocin (STZ) injection and high glucose/fat diet feeding, rats were administered intragastrically with SAC. Then, cardiac systolic/diastolic function was evaluated by detecting left ventricular systolic pressure (LVSP), maximal rate of left ventricular pressure rise (+LVdp/dtmax), and fall (-LVdp/dtmax), heart rate (HR), left ventricular ejection fraction (EF), LV fractional shortening (FS) and left ventricular end-diastolic pressure (LVEDP). Masson's and TUNEL staining were used to assess fibrosis and cardiomyocyte apoptosis. RESULTS: DCM rats exhibited impaired cardiac systolic/diastolic function manifested by decreasing LVSP, + LVdp/dtmax, -LVdp/dtmax, HR, EF and FS, and increasing LVEDP. Intriguingly, traditional Chinese medicine SAC alleviated the above-mentioned symptoms, indicating a potential role in improving cardiac function. Masson's staining substantiated that SAC antagonized the increased collagen deposition and interstitial fibrosis area and the elevations in protein expression of fibrosisrelated collagen I and fibronectin in heart tissues of DCM rats. Furthermore, TUNEL staining confirmed that traditional Chinese medicine SAC also attenuated cardiomyocyte apoptosis in DCM rats. Mechanically, DCM rats showed the aberrant activation of the TGF-ß/Smad signaling, which was inhibited after SAC. CONCLUSION: SAC may exert cardiac protective efficacy in DCM rats via the TGF-ß/Smad signaling, indicating a new promising therapeutic approach for DCM.

Iodine-doped TiO2 nanotube coatings: a technique for enhancing the antimicrobial properties of titanium surfaces against Staphylococcus aureus.

BACKGROUND: Implant-related infections are a challenging complication of orthopedic surgery, primarily due to the formation of bacterial biofilms on the implant surface. An antibacterial coating for titanium implants was developed to provide novel insights into the prevention and treatment of implant-related infections. METHODS: Titanium plates were coated with TiO2 nanotubes by anodization, and iodine was doped onto the coating via electrophoretic deposition. The obtained plates were characterized using a range of analytical techniques. Subsequently, Staphylococcus aureus was inoculated onto the surfaces of untreated titanium plates (control group), TiO2-nanocoated titanium plates (TiO2 group), and iodine-doped TiO2-nanocoated titanium plates (I-TiO2 group) to compare their antibacterial properties. RESULTS: Twenty-four hour in vitro antimicrobial activity test of the I-TiO2 group against Staphylococcus aureus was superior to those of the other groups, and this difference was statistically significant (P < 0.05). CONCLUSIONS: This coating technology provides a new theoretical basis for the development of anti-infective implants against Staphylococcus aureus in orthopedics.

Fractional-order iterative learning control for fractional-order systems with initialization non-repeatability.

The effect of initialization non-repeatability on iterative learning control performance for fractional-order systems has not been sufficiently investigated. It is a hidden deficiency that leads directly to the breaking of perfect tracking conditions in both theoretical analysis and real-world applications. Therefore, under the framework of general fractional-order nonlinear systems, this paper proposes an open-close loop Dα-type iterative learning control scheme based on system preconditioning and strictly derives two convergence conditions. By applying the preconditioning optimization strategy based on the short-memory principle, the tracking error due to initialization nonrepetition can converge to any desired range. Compared with the existing results, the proposed iteration scheme fully considers the complexity of the initialization and initial conditions of fractional-order systems, and provides several practical preconditioning methods to improve the tracking efficiency. Two numerical examples are presented to validate the above conclusions.

Postoperative urinary leakage after bilateral totally extraperitoneal herniorrhaphy in a patient with a healed cystostomy and appendectomy: A case report.

We report a case of postoperative urinary leakage after bilateral laparoscopic totally extraperitoneal (TEP) herniorrhaphy. A man in his upper 80s with a healed cystostomy and appendectomy underwent bilateral TEP herniorrhaphy. Urinary leakage was noted by ultrasound examination 4 days after bilateral TEP. Cystography and computed tomography conclusively confirmed a 6-mm extraperitoneal fistula at the site of the previous cystostomy. The fistula involved the anterior bladder wall and was associated with an extended urinoma. The patient was treated by indwelling catheterization using a Foley catheter and repeated ultrasound-guided puncture and aspiration of the inguinal effusion at the bedside. The patient was completely healed 69 days after the operation with no mesh infection or bladder dysfunction. We believe that urinary leakage is possible after TEP herniorrhaphy in patients with a healed suprapubic cystostomy. Therefore, indwelling catheterization using a Foley catheter should be implemented before surgery, and the Foley catheter can be removed within 1 week after surgery if no postoperative urinary leakage is observed. A history of suprapubic cystotomy should not be regarded as a contraindication for TEP surgery. This is the first report of urinary leakage after bilateral TEP herniorrhaphy in a patient with a healed cystostomy and appendectomy.

Comparative effectiveness of three treatment options for slade and dodds grade III-IV scaphoid nonunion: a retrospective study.

OBJECTIVE: To compare the clinical efficacy of open debridement screw fixation combined with bone grafting, percutaneous screw fixation, and percutaneous screw fixation combined with injection of platelet-rich plasma (PRP) for the treatment of Slade and Dodds Grade III to IV scaphoid nonunion (SNU). METHODS: This retrospective study included patients with Grade III (25 patients) and Grade IV (28 patients) SNU. They were treated with open surgery bone grafting and internal fixation (group A), percutaneous screw fixation (group B) or percutaneous screw fixation and PRP injection (group C) from January 2015 to May 2020. The fracture consolidation rate, VAS score, and Mayo wrist function score were compared across the three groups. RESULTS: The consolidation rate was not significantly different among the three groups for both Grade III and IV SNU. However, patients in group C reported significantly less pain and better wrist function 7 days after surgery compared to group A and B, for both nonunion grades. At 3 months after surgery, group C had significantly better VAS and Mayo wrist scores compared to group A for both nonunion grades, and compared to group B for Grade IV SNU. At 6 and 12 months after surgery, patients with Grade IV SNU in groups A and C had significantly better VAS and Mayo wrist scores compared to group B. CONCLUSION: This study suggests that percutaneous screw fixation with PRP injection could be a more effective method for treating Grade IV SNU. This approach may reduce postoperative wrist pain and improve wrist function in the early stages after surgery for patients with both Grade III and IV SNU. TYPE OF STUDY/LEVEL OF EVIDENCE: IV.

Bioinformatics analyses for the identification of tumor antigens and immune subtypes of gastric adenocarcinoma.

Background: Although mRNA vaccines have been effective against multiple cancers, their efficacy against stomach adenocarcinoma (STAD) remains undefined. Immunotyping can indicate the comprehensive immune status in tumors and their immune microenvironment, which is closely associated with therapeutic response and vaccination potential. The aim of this study was to identify potential antigens in STAD for mRNA vaccine development, and further distinguish immune subtypes of STAD to construct an immune landscape for selecting suitable patients for vaccination. Methods: The gene expression and clinicopathological features of patients with gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Program (GTEx). 729 samples from GSE66229 and GSE84437 were downloaded through GEO and were used as the validation cohorts. Differential gene expression, genetic alterations and prognosis were analyzed using the R package, cBioPortal program and Kaplan-Meier. The relationship between tumor antigens and immune cells was evaluated and plotted by TIMER. ConsensusClusterPlus was used for consistency matrix construction and data clustering, and graph learning-based dimensional reduction was used to depict immune landscape. WGCNA was used to estimate the relationship between the color modules and immune subtypes. Results: Two overexpressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in STAD, including RAI14 and NREP. The immune subtypes showed distinct molecular, cellular and clinical characteristics. IS1 and IS2 exhibited immune-activated phenotypes and correlated to better survival compared to IS3, while IS3 tumors was immunologically cold. Immunogenic cell death modulators, immune checkpoints, and CA125, and CEA were also differentially expressed among the three immune subtypes. Finally, the immune landscape of STAD showed a high degree of heterogeneity between individual patients. Conclusion: RAI14 and NREP are potential antigens for developing anti-STAD mRNA vaccine, and patients with IS1 and IS3 tumors may be suitable for vaccination.

Effects of Ruanmailing in Blocking Early Stages of Atherosclerosis by TNF-α Regulation via Kir2.1.

Objective: Ruanmailing oral solution consists of 16 herbs, has anti-lipid peroxidation activity, protects vascular endothelial cells, and improves vascular elasticity. It is an effective drug for the treatment of atherosclerosis (AS). The objective of this study was to investigate the mechanism underlying the antiatherosclerotic effects of Ruanmailing oral solution. Methods: Macrophages were isolated, cultured, and divided into the macrophage control; macrophage foam cell; and low-, medium-, and high-concentration Ruanmailing groups. Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay, and the expression levels of inward-rectifier potassium ion channel 2.1 (Kir2.1) and tumor necrosis factor (TNF)-α were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. Results: CCK-8 assay results showed that the tested concentrations of Ruanmailing solution did not affect macrophage proliferation. RT-PCR and Western blot assays indicated that TNF-α expression increased significantly with the formation of macrophage foam cells (P < 0.05). In addition, significant decreases in Kir2.1 and TNF-α expression were observed following treatment with various concentrations of Ruanmailing (P < 0.05). Conclusion: Based on the results, Ruanmailing affects macrophage foam cell formation by regulating Kir2.1 expression, which in turn reduces TNF-α expression and exerts antiatherosclerotic effects. These findings provide a scientific basis for the use of traditional Chinese medicine for AS treatment.

Unsupervised Learning with Generative Adversarial Network for Automatic Tire Defect Detection from X-ray Images.

Automatic defect detection of tire has become an essential issue in the tire industry. However, it is challenging to inspect the inner structure of tire by surface detection. Therefore, an X-ray image sensor is used for tire defect inspection. At present, detection of defective tires is inefficient because tire factories commonly conduct detection by manually checking X-ray images. With the development of deep learning, supervised learning has been introduced to replace human resources. However, in actual industrial scenes, defective samples are rare in comparison to defect-free samples. The quantity of defective samples is insufficient for supervised models to extract features and identify nonconforming products from qualified ones. To address these problems, we propose an unsupervised approach, using no labeled defect samples for training. Moreover, we introduce an augmented reconstruction method and a self-supervised training strategy. The approach is based on the idea of reconstruction. In the training phase, only defect-free samples are used for training the model and updating memory items in the memory module, so the reproduced images in the test phase are bound to resemble defect-free images. The reconstruction residual is utilized to detect defects. The introduction of self-supervised training strategy further strengthens the reconstruction residual to improve detection performance. The proposed method is experimentally proved to be effective. The Area Under Curve (AUC) on a tire X-ray dataset reaches 0.873, so the proposed method is promising for application.

Circ_0001721 enhances doxorubicin resistance and promotes tumorigenesis in osteosarcoma through miR-758/TCF4 axis.

BACKGROUND: Osteosarcoma (OS) is a common type of bone malignancy that often occurs in children and adolescents. Chemoresistance is a huge barrier to cancer therapy. This study aimed to investigate the role and potential mechanism of circ_0001721 in doxorubicin (DXR) resistance and OS development. METHODS: The levels of circ_0001721, miR-758 and transcription factor 4 (TCF4) were detected by quantitative real-time polymerase chain reaction or western blot assay. Cell Counting Kit-8 (CCK-8) assay was used to calculate the half inhibition concentration (IC50) of DXR and assess cell viability. Cell migration and invasion were evaluated by transwell assay. Cell apoptosis was monitored by flow cytometry. The levels of multidrug resistance-related and Wnt/ß-catenin pathway-related proteins were measured by western blot assay. The interaction among circ_0001721, miR-758 and TCF4 were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation assay or RNA pull-down assay. The xenograft model was established to analyze tumor growth in vivo. RESULTS: Circ_0001721 and TCF4 were upregulated, whereas miR-758 was down-regulated in DXR-resistant OS tissues and cells. Circ_0001721 silence reduced DXR resistance of KHOS/DXR and MG63/DXR cells. Circ_0001721 regulated DXR resistance via sponging miR-758. Moreover, miR-758 modulated DXR resistance by targeting TCF4. Besides, circ_0001721 knockdown inhibited tumor growth in vivo. CONCLUSION: Circ_0001721 potentiated DXR resistance and facilitated the progression of OS by regulating miR-758/TCF4 axis, which provides promising therapeutic targets for OS treatment.

Small-Molecule Inhibitors of the Coronavirus Spike: ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2.

Inhibitors of the protein-protein interaction (PPI) between the SARS-CoV-2 spike protein and human ACE2 (hACE2), which acts as a ligand-receptor pair that initiates the viral attachment and cellular entry of this coronavirus causing the ongoing COVID-19 pandemic, are of considerable interest as potential antiviral agents. While blockade of such PPIs with small molecules is more challenging than that with antibodies, small-molecule inhibitors (SMIs) might offer alternatives that are less strain- and mutation-sensitive, suitable for oral or inhaled administration, and more controllable/less immunogenic. Here, we report the identification of SMIs of this PPI by screening our compound library focused around the chemical space of organic dyes. Among promising candidates identified, several dyes (Congo red, direct violet 1, Evans blue) and novel druglike compounds (DRI-C23041, DRI-C91005) inhibited the interaction of hACE2 with the spike proteins of SARS-CoV-2 as well as SARS-CoV with low micromolar activity in our cell-free ELISA-type assays (IC50's of 0.2-3.0 µM), whereas control compounds, such as sunset yellow FCF, chloroquine, and suramin, showed no activity. Protein thermal shift assays indicated that the SMIs of interest identified here bind SARS-CoV-2-S and not hACE2. While dyes seemed to be promiscuous inhibitors, DRI-C23041 showed some selectivity and inhibited the entry of two different SARS-CoV-2-S expressing pseudoviruses into hACE2-expressing cells in a concentration-dependent manner with low micromolar IC50's (6-7 µM). This provides proof-of-principle evidence for the feasibility of small-molecule inhibition of PPIs critical for SARS-CoV-2 attachment/entry and serves as a first guide in the search for SMI-based alternative antiviral therapies for the prevention and treatment of diseases caused by coronaviruses in general and COVID-19 in particular.

The importance of preoperative T1 slope for determining proper postoperative C2-7 Cobb's angle in patients undergoing cervical reconstruction.

BACKGROUND: This study aimed to explore the relationship among different cervical sagittal parameters in asymptomatic volunteers and the correlation between surgical efficacy and difference of presumed and actual postoperative C2-7 Cobbs's angle (C2-7COBB), which was calculated based on preoperative T1 slope (T1S) in patients undergoing cervical reconstruction. METHODS: In total, 158 inpatients with cervical spondylosis and 274 asymptomatic volunteers were retrospectively reviewed. Cervical sagittal parameters, such as C2-7COBB, T1S, thoracic inlet angle (TIA), and neck tilt (NT), were compared. Then, the correlation among these parameters was analyzed in asymptomatic volunteers, and a regression equation between T1S and C2-7COBB was established and used to analyze the correlation among the Japanese Orthopaedic Association (JOA) score improvement, the sagittal parameters, and the difference between presumed and actual postoperative C2-7COBB in patients after cervical reconstruction. RESULTS: The mean T1S, C2-7COBB, and TIA were significantly decreased in patients (P < 0.01). T1S and NT had a strong correlation with TIA (P < 0.01). T1S demonstrated a moderate correlation with C2-7COBB in asymptomatic volunteers (r = 0.569, P < 0.01). A regression equation had been established as C2-7COBB = 0.742 × T1S - 0.866. The mean C2-7COBB and JOA score improved significantly (P < 0.05) postoperatively. Moreover, the JOA improvement rate showed a significant negative correlation with the difference in the presumed and actual postoperative C2-7COBB (r = - 0.696, P < 0.01). CONCLUSION: Our study successfully established a regression equation for calculating postsurgical C2-7COBB based on the correlation between T1S and C2-7COBB in asymptomatic volunteers. The regression equation could be used for guiding surgeons to accomplish an ideal postsurgical C2-7COBB for patients with cervical spondylosis.

Biomechanics of the effect of subaxial cervical spine degeneration on atlantoaxial complex in idiopathic retro-odontoid pseudotumor development.

OBJECTIVES: Retro-odontoid pseudotumor (ROP), with no rheumatoid arthritis, atlantoaxial instability, or other primary diseases, is defined as idiopathic retro-odontoid pseudotumor (IROP). Cervical spine degeneration is associated with IROP development. This study aims to evaluate the effect of cervical spine degeneration on the atlantoaxial complex and find the possible biomechanical mechanism of IROP development. METHODS: This study was performed using a three-dimensional (3D) finite element (FE) analysis. A degenerated FE model (FEM) and five operation FEMs (C1-C2 fusion, C0-C2 fusion, C0-C3 fusion, C0-C4 fusion, and C1 posterior arch resection) were established based on a normal 3D FEM of the cervical spine including C0-T1 with the main ligaments and muscles. The parameters, including the C1-C2 range of motions (ROMs) and odontoid-related ligaments' stresses in degenerated and operation FEMs, were obtained and compared with those in normal FEM. RESULTS: Compared to normal FEM, degenerated FEM had reduced C3-C7 ROMs and increased C1-C2 ROMs and odontoid-related ligaments' stresses. After internal fixation, C1-C2 ROMs and most odontoid-related ligaments' stresses were greatly decreased, but with no significant differences among C0-C2, C0-C3, C0-C4, and C1-C2 fusion models. For the C1 posterior arch resection model, C1-C2 ROMs and most odontoid-related ligaments' stresses increased, compared with normal FEM. CONCLUSIONS: Cervical spine degeneration plays an important part in IROP development in biomechanics. Atlantoaxial complex compensates for cervical spine degeneration, with increased C1-C2 ROMs and odontoid-related ligaments' stresses. Atlantoaxial fusion or short segmental occipitocervical fusion can effectively reduce the stress and should be considered in IROP treatment.

Identification of hub genes and construction of transcriptional regulatory network for the progression of colon adenocarcinoma hub genes and TF regulatory network of colon adenocarcinoma.

The aim of this study was to identify key genes related to the progression of colon adenocarcinoma (COAD), and to investigate the regulatory network of hub genes and transcription factors (TFs). Dataset GSE20916 including 44 normal colon, 55 adenoma, and 36 adenocarcinoma tissue samples was used to construct co-expression networks via weighted gene co-expression network. Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for the objective module were performed using the online Database for Annotation, Visualization and Integrated Discovery. Hub genes were identified by taking the intersection of differentially expressed genes between dataset GSE20916 and GSE39582 and validated using The Cancer Genome Atlas (TCGA) database. The correlations between microRNA (miRNA) and hub genes were analyzed using the online website StarBase. Cytoscape was used to establish a regulatory network of TF-miRNA-target gene. We found that the orange module was a key module related to the tumor progression in COAD. In datasets GSE20916 and GSE39582, a total of eight genes (BGN, SULF1, COL1A1, FAP, THBS2, CTHRC1, COL5A2, and COL1A2) were selected, which were closely related with patients' survivals in TCGA database and dataset GSE20916. COAD patients with higher expressions of each hub gene had a worse prognosis than those with lower expressions. A regulatory network of TF-miRNA-target gene with 144 TFs, 26 miRNAs, and 7 hub genes was established, including model KLF11-miR149-BGN, TCEAL6-miR29B2-COL1A1, and TCEAL6-miR29B2-COL1A2. In conclusion, during the progression of COAD, eight core genes (BGN, SULF1, COL1A1, FAP, THBS2, CTHRC1, COL5A2, and COL1A2) play vital roles. Regulatory networks of TF-miRNA-target gene can help to understand the disease progression and optimize treatment strategy.

Comparison of Two Posterior Three-Point Fixation Techniques for Treating Reducible Atlantoaxial Dislocation.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To compare the outcomes of C1-C2 transarticular screw combined with C1 laminar hook (TAS+C1H) and C1-C2 transarticular screw combined with modified Gallie technique (TAS+G) for treating reducible atlantoaxial dislocation (AAD). SUMMARY OF BACKGROUND DATA: Both TAS+C1H and TAS+G fixation were 3-point fixation techniques for AAD. TAS+C1H technique was comparable to TAS+G technique in biomechanics. However, it is unknown whether it can achieve same outcomes as TAS+G technique. METHODS: Data of the 63 patients who underwent TAS+C1H or TAS+G fixation and fusion because of AAD were retrospectively reviewed. Bone fusion time was recorded. The outcomes evaluated by visual analog scale score for neck pain (VASSNP), Nurick scale, neck stiffness (none/mild/severe), patient satisfaction, and Neck Disability Index (NDI) were compared between two groups. RESULTS: At the final follow-up, bone graft fusion rates were 100% in both groups (P > 0.05). Nurick scales were significantly improved in both groups (P < 0.05), but with no significant differences between groups (P > 0.05). There were no significant differences between two groups in VASSNP, neck stiffness, patient satisfaction, or NDI (all P > 0.05). There were no complications related to the surgical approach and instrumentation in either group. CONCLUSION: Both TAS+C1H and TAS+G fixation were effective in the treatment of reducible AAD. TAS+C1H was safer than TAS+G because it could potentially reduce the risk of spinal cord and venous plexus injury associated with sublaminar cables. LEVEL OF EVIDENCE: 3.

Design, Synthesis, and Evaluation of Novel Immunomodulatory Small Molecules Targeting the CD40⁻CD154 Costimulatory Protein-Protein Interaction.

We report the design, synthesis, and testing of novel small-molecule compounds targeting the CD40⁻CD154 (CD40L) costimulatory interaction for immunomodulatory purposes. This protein-protein interaction (PPI) is a TNF-superfamily (TNFSF) costimulatory interaction that is an important therapeutic target since it plays crucial roles in the activation of T cell responses, and there is resurgent interest in its modulation with several biologics in development. However, this interaction, just as all other PPIs, is difficult to target by small molecules. Following up on our previous work, we have now identified novel compounds such as DRI-C21091 or DRI-C21095 that show activity (IC50) in the high nanomolar to low micromolar range in the binding inhibition assay and more than thirty-fold selectivity versus other TNFSF PPIs including OX40⁻OX40L, BAFFR-BAFF, and TNF-R1-TNFα. Protein thermal shift (differential scanning fluorimetry) assays indicate CD154 and not CD40 as the binding partner. Activity has also been confirmed in cell assays and in a mouse model (alloantigen-induced T cell expansion in a draining lymph node). Our results expand the chemical space of identified small-molecule CD40⁻CD154 costimulatory inhibitors and provide lead structures that have the potential to be developed as orally bioavailable immunomodulatory therapeutics that are safer and less immunogenic than corresponding biologics.

Small-Molecule Inhibitors of the CD40-CD40L Costimulatory Protein-Protein Interaction.

Costimulatory interactions are required for T cell activation and development of an effective immune response; hence, they are valuable therapeutic targets for immunomodulation. However, they, as all other protein-protein interactions, are difficult to target by small molecules. Here, we report the identification of novel small-molecule inhibitors of the CD40-CD40L interaction designed starting from the chemical space of organic dyes. For the most promising compounds such as DRI-C21045, activity (IC50) in the low micromolar range has been confirmed in cell assays including inhibition of CD40L-induced activation in NF-κB sensor cells, THP-1 myeloid cells, and primary human B cells as well as in murine allogeneic skin transplant and alloantigen-induced T cell expansion in draining lymph node experiments. Specificity versus other TNF-superfamily interactions (TNF-R1-TNF-α) and lack of cytotoxicity have also been confirmed at these concentrations. These novel compounds provide proof-of-principle evidence for the possibility of small-molecule inhibition of costimulatory protein-protein interactions, establish the structural requirements needed for efficient CD40-CD40L inhibition, and serve to guide the search for such immune therapeutics.

Comparison of Outcomes Between C1-C2 Screw-Hook Fixation and C1-C2 Screw-Rod Fixation for Treating Reducible Atlantoaxial Dislocation.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To compare the outcomes of C1-C2 transarticular screw with C1 laminar hook (TAS + C1H) fixation and C1 trans-arch lateral mass screw with C2 pedicle screw (C1TLMS + C2PS) fixation in the treatment of reducible atlantoaxial dislocation (AAD). SUMMARY OF BACKGROUND DATA: TAS + C1H is comparable to TAS with posterior wiring techniques and superior to C1 lateral mass screw combined with C2 pedicle screw (C1LMS + C2PS) in biomechanics. There were, however, few studies analyzing the differences in outcomes between TAS + C1H technique and modified C1LMS + C2PS technique (C1TLMS + C2PS) for treating AAD. METHODS: Data of 30 patients with reducible AAD treated by TAS + C1H fixation and another 30 cases treated by C1TLMS + C2PS fixation were retrospectively analyzed. Bone fusion time was recorded. The outcomes evaluated by American Spinal Injury Association impairment scale, visual analog scale score for neck pain, neck stiffness (none/mild/severe), patient satisfaction, and Neck Disability Index (NDI) were compared between two groups. RESULTS: There were no complications related to the surgical approach and instrumentation in either group. At the final follow-up, bone graft fusion rates were 100% in both the TAS + C1H fixation group and the C1TLMS + C2PS fixation group (P > 0.05). The neurological status evaluated by American Spinal Injury Association impairment scale were greatly improved in both screw-hook group (P < 0.001) and screw-rod group (P < 0.001), but with no significant differences between groups (P > 0.05). There were no significant differences between two groups in visual analog scale score for neck pain, neck stiffness, patient satisfaction, or Neck Disability Index (all P > 0.05). CONCLUSION: C1TLMS + C2PS fixation was comparable to TAS + C1H fixation in fusion rate and functional outcomes for treating reducible AAD. To reduce the risk of vertebral artery injury, computed tomography scan, and reconstruction should be done to analyze vertebral artery course and C1-C2 anatomic structures before operation. LEVEL OF EVIDENCE: 3.

Effects of Shenqi Fuzheng injection on Fas/FasL protein expression levels in the cardiomyocytes of a mouse model of viral myocarditis.

The aim of the present study was to examine the effects of Shenqi Fuzheng injection (SFI) on Fas and FasL protein expression levels in the cardiomyocytes of mice with viral myocarditis (VMC) and to explore the underlying anti-apoptotic mechanisms. A total of 120 male BALB/c mice were randomly divided into five groups as follows: Blank control group, model group, ribavirin group, low-dose SFI group and high-dose SFI group. The VMC model was established by the injection of coxsackievirus group B type 3 and saline, ribavirin or SFI was administered 30 min later. Cardiac samples were harvested from mice in each group on days 3, 10 and 30. Apoptosis of cardiac cells was examined using terminal deoxynucleotidyl transferase dUTP nick-end labeling, and Fas and FasL protein expression levels were detected using immunohistochemistry. Myocardial apoptosis and Fas/FasL protein expression levels were significantly increased in the model group, as compared with the blank group (P<0.01), whereas the apoptotic index (AI) and Fas/FasL protein expression levels of cardiac cells in the high-dose SFI group were significantly decreased compared with those in the model group on day 10 (acute phase; P<0.01). The AI and Fas/FasL protein expression levels of cardiac cells in the low- and high-dose SFI groups were also significantly decreased on day 30 (chronic phase; P<0.01); however, no differences between the high- and low-dose groups were detected. In conclusion, SFI relieves VMC via the downregulation of Fas and FasL protein expression and the inhibition of cell apoptosis.

New Posterior Atlantoaxial Restricted Non-Fusion Fixation for Atlantoaxial Instability: A Biomechanical Study.

BACKGROUND: Loss of axial rotation and lateral bending after atlantoaxial fusion reduces a patient's quality of life. Therefore, effective, nonfusion fixation alternatives are needed for atlantoaxial instability. OBJECTIVE: To evaluate the initial stability and function of posterior atlantoaxial restricted nonfusion fixation (PAARNF), a new protocol, using cadaveric cervical spines compared with the intact state, destabilization, and posterior C1-C2 rod fixation. METHODS: Cervical areas C0 through C3 were used from 6 cadaveric spines to test flexion-extension, lateral bending, and axial rotation range of motion (ROM). With the use of a machine, 1.5-Nm torque at a rate of 0.1 Nm/s was used and held for 10 seconds. The specimens were loaded 3 times, and data were collected in the third cycle and tested in the following sequence: (1) intact, (2) destabilization (using a type II odontoid fracture model), (3) destabilization with PAARNF (PAARNF group), and (4) rod implantation (rod group). The order of tests for the PAARNF and rod groups was randomly assigned. RESULTS: The average flexion-extension ROM in the PAARNF group was 7.44 ± 2.05°, which was significantly less than in the intact (P = .00) and destabilization (P = .00) groups but not significantly different from that of the rod group (P = .07). The average lateral bending ROM (10.59 ± 2.33°; P = .00) and axial rotation ROM (38.79 ± 13.41°; P = .00) of the PAARNF group were significantly greater than in the rod group. However, the values of the PAARNF group showed no significant differences compared with those of the intact group. CONCLUSION: PAARNF restricted atlantoaxial flexion-extension but preserved axial rotation and lateral bending at the atlantoaxial joint in a type II odontoid fracture model. However, it should not be used clinically until further studies have been performed to test the long-term effects of this procedure.

Subaxial Cervical Intradiscal Pressure and Segmental Kinematics Following Atlantoaxial Fixation in Different Angles.

OBJECTIVE: To evaluate in a comprehensive biomechanical study the influences of fixed C1-C2 and different C1-C2 angles on the range of motion (ROM) and the intradiscal pressure (IDP) of subaxial cervical spine. METHODS: We simulated three-dimensional cervical motions on 8 human specimens with C1-C2 fixed in 3 different angles (neutral position, neutral position -10°, neutral position +10°) following intact analysis in the material test system. The ROM changes of each motion segment and the IDP changes of 4 subaxial motion segments (C2-C3, C3-C4, C4-C5, and C5-C6) were monitored. RESULTS: ROM change patterns at all subaxial segments were similar. Fixed C1-C2 led to a significant ROM increase relative to the intact condition during flexion/extension testing. A larger C1-C2 angle (neutral position +10°) caused an additional ROM increase during flexion, whereas a smaller C1-C2 angle (neutral position -10°) induced a further ROM increase during extension. Axial rotation testing revealed the most striking and similar ROM increases in the instrumented groups relative to the intact group. Lateral bending testing did not reveal significant ROM change between the instrumented groups and the intact group. For IDP analysis, C1-C2 fixed in a larger angle (neutral position +10°) caused significant IDP increases at the C2-C3, C3-C4, and C4-C5 levels during flexion. CONCLUSIONS: To maintain a physiologic sagittal alignment of subaxial cervical spine, C1-C2 should be fixed in the neutral position or a relatively smaller angle instead of a more lordotic position.