Integrated investigation of DNA methylation, gene expression and immune cell population revealed immune cell infiltration associated with atherosclerotic plaque formation.

BACKGROUND: The clinical consequences of atherosclerosis are significant source of morbidity and mortality throughout the world, while the molecular mechanisms of the pathogenesis of atherosclerosis are largely unknown. METHODS: In this study, we integrated the DNA methylation and gene expression data in atherosclerotic plaque samples to decipher the underlying association between epigenetic and transcriptional regulation. Immune cell classification was performed on the basis of the expression pattern of detected genes. Finally, we selected ten genes with dysregulated methylation and expression levels for RT-qPCR validation. RESULTS: Global DNA methylation profile showed obvious changes between normal aortic and atherosclerotic lesion tissues. We found that differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were highly associated with atherosclerosis by being enriched in atherosclerotic plaque formation-related pathways, including cell adhesion and extracellular matrix organization. Immune cell fraction analysis revealed that a large number of immune cells, especially macrophages, activated mast cells, NK cells, and Tfh cells, were specifically enriched in the plaque. DEGs associated with immune cell fraction change showed that they were mainly related to the level of macrophages, monocytes, resting NK cells, activated CD4 memory T cells, and gamma delta T cells. These genes were highly enriched in multiple pathways of atherosclerotic plaque formation, including blood vessel remodeling, collagen fiber organization, cell adhesion, collagen catalogic process, extractable matrix assembly, and platelet activation. We also validated the expression alteration of ten genes associated with infiltrating immune cells in atherosclerosis. CONCLUSIONS: In conclusion, these findings provide new evidence for understanding the mechanisms of atherosclerotic plaque formation, and provide a new and valuable research direction based on immune cell infiltration.

Preliminary results of iliosacral screws and plate combination in the management of tile B3 pelvic fractures: A retrospective case series.

OBJECTIVE: The aim of this study was to present preliminary results and experience with iliosacral screws and plate combination (horizontal triangular osteosynthesis, HTO) in the management of Tile B3 pelvic fractures. METHODS: In this retrospective study, 26 patients (18 male, 8 female; mean age = 46, age range = 31-58 years) who were treated with horizontal triangular osteosynthesis using the combination of bilateral percutaneous iliosacral screws and transiliac plates due to Tile B3 pelvic fractures in our institution were included. The accompanying symptoms, blood loss, operation time , fracture healing time, and postoperative complications were observed and recorded. Patients were followed up retrospectively with routine post-operation visits for clinical and radiographic examination. The reduction quality was evaluated according to Matta criterion. Clinical and nerve function outcomes were evaluated by Majeed and Gibbons criterion. RESULTS: The mean follow-up time was 15 months (range = 12-21 months). The mean blood loss and operation time were 24.6 ± 6.7mL and 30.5 ± 3.47 mins, respectively. Patients experienced early weight-bearing ability and no fracture reduction loss. Due to Matta criterion for fracture reduction, the results were excellent in 16 cases, good in 9 cases, and fair in 1 case. Due to Majeed functional scoring at the last follow-up, the results were excellent in 17 cases, good in 9 cases. Of 3 patients in whom neurologic impairment was detected preoperatively, 2 achieved complete recovery, and 1 achieved partial improvement postoperatively. CONCLUSION: As a new surgical concept in the management of Tile B3 pelvic fractures, HTO seems to provide the following advantages: horizontal triangular fixation, minimally invasive incisions, less blood loss, and permitting early weight-bearing ability. However, there still exist several problems regarding the technique and the option of implants. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

Neutrophil-to-Lymphocyte Ratios Are Closely Associated With the Severity and Course of Non-mild COVID-19.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is spreading worldwide. Measuring the prevention and control of the disease has become a matter requiring urgent focus. Objective: Based on coronavirus disease 2019 (COVID-19) clinical data from Wuhan, we conducted an in-depth analysis to clarify some of the pathological mechanisms of the disease and identify simple measures to predict its severity early on. Methods: A total of 230 patients with non-mild COVID-19 were recruited, and information on their clinical characteristics, inflammatory cytokines, and T lymphocyte subsets was collected. Risk factors for severity were analyzed by binary logistic regression, and the associations of neutrophil-to-lymphocyte ratios (N/LRs) with illness severity, disease course, CT grading, inflammatory cytokines, and T lymphocyte subsets were evaluated. Results: Our results showed that the N/LRs were closely related to interleukin (IL)-6 and IL-10 (P < 0.001, P = 0.024) and to CD3+ and CD8+ T lymphocytes (P < 0.001, P = 0.046). In particular, the N/LRs were positively correlated with the severity and course of the disease (P = 0.021, P < 0.001). Compared to the values at the first test after admission, IL-6 and IL-10 were significantly decreased and increased, respectively, as of the last test before discharge (P = 0.006, P < 0.001). More importantly, through binary logistic regression, we found that male sex, underlying diseases (such as cardiovascular disease), pulse, and N/LRs were all closely related to the severity of the disease (P = 0.004, P = 0.012, P = 0.013, P = 0.028). Conclusions: As a quick and convenient marker of inflammation, N/LRs may predict the disease course and severity level of non-mild COVID-19; male sex, cardiovascular disease, and pulse are also risk factors for the severity of non-mild COVID-19.

Risk-adapted Treatment Strategy For COVID-19 Patients.

BACKGROUND: There are no clear expert consensus or guidelines on how to treat 2019 coronavirus disease (COVID-19). The objective of this study is to investigate the short-term effect of risk-adapted treatment strategy on patients with COVID-19. METHODS: We collected the medical records of 55 COVID-19 patients for analysis. We divided these patients into mild, moderate and severe groups, and risk-adapted treatment approaches were given according to the illness severity. RESULTS: Twelve patients were in mild group and 22 were in moderate group (non-severe group, n=34), and 21 patients were in severe group. At the end of the first two weeks after admission, clinical manifestations had completely despeared in 31(91.2%)patients in non-severe group, and 18(85.7%) patients in severe group (p=0.85). Both groups had a satisfied chest CT imaging recovery, which includes 22(64.7%) patients in non-severe group and 12(57.1%) patients in severe group recovered at least 50% of the whole leisions in the first week, and 28(82.4%) and 16(76.2%) recovered at least 75% in the second week, respectively. There were no significant differences in SARS-CoV-2 nucleic acid negativity (p=0.92). There were also no significant differences in the levels of SARS-CoV-2-IgM and IgG antibody production between the two groups (p=0.13, 0.62). There were 45 cases were discharged from the hospital, and no patients died at the time of this clinical analysis. CONCLUSIONS: Risk-adapted treatment strategy was associated with significant clinical manifestations alleviation and clinical imaging recovery. In severe COVID-19 patients, early and short-term use of low-dose methylprednisolone was beneficial and did not delay SARS-CoV-2 nucleic acid clearance and influence IgG antibody production.

T-plate fixation for unstable proximal clavicula fractures.

OBJECTIVE: The aim of this study was to evaluate the clinical results of T-plate fixation and anterior sternoclavicular ligament repair in proximal clavicle fractures. METHODS: Between August 2013 and August 2016, a total 12 patients (10 men and 2 women; mean age: 44.1 ± 9.1 years (range, 25-59 years)) with unstable proximal clavicle fractures (Throckmorton, type D) were treated with T-type plate fixation, bridging the sternoclavicular joint, and anterior sternoclavicular ligament repair. Average operative time, associated injuries, postoperative complications, postoperative fracture healing time and follow-up time were recorded. The outcomes were evaluated with radiographic assessment, visual analog scale (VAS) pain score and Rockwood SCJ scoring system. All the patients were evaluated on postoperative 3rd, 6th, and 12th months. RESULTS: The average surgery time was 78.0 ± 8.47 minutes while fracture healing time was 4.51 ± 0.95 months. According to Rockwood SCJ scoring system, 9 cases (75%) were in excellent, 2 cases (16.7%) in good and 1 case (8.3%) in fair condition at 12 months follow-up. The average Rockwood SCJ score was 7.7 ± 0.75 preoperatively, 12.7 ± 0.86 by 3 months, 13.0 ± 0.73 by 6 months and 13.3 ± 0.49 by 12 months. The VAS pain score was 7.9 ± 1.15 (preoperative score), 3.4 ± 1.52 (3 months follow-up), 3.0 ± 1.32 (6 months follow-up) and 2.1 ± 1.07 (12 months follow-up). The VAS and Rockwood SCJ scores were significantly improved postoperatively (p < 0.05). There was no intraoperative complication, while one patient had redislocation of the sternoclavicular joint after implant removal. CONCLUSION: T-type plate fixation with anterior sternoclavicular ligament repair might be a reliable and effective treatment method in unstable proximal clavicle fractures (type D) with few complications and satisfactory clinical results after 12 months follow-up. LEVEL OF EVIDENCE: Level IV, therapeutic study.

[Correlation between Gan Depression Qi Stagnation Syndrome and Thyroid Stimulating Hormone Level in Adolescent Polycystic Ovary Syndrome Patients].

Objective To observe the distribution features of Gan depression qi stagnation syndrome (GDQSS) , and to analyze the correlation between GDQSS scores and thyroid stimulating hormone (TSH) level in adolescent polycystic ovary syndrome (PCOS) patients. Methods Disease location and disease nature were syndrome identified in PCOS outpatients confirmed at Department of Gynecology, Ningbo Municipal Hospital of TCM. Totally 110 patients in line with GDQSS were graded by GDQSS score from low to high. GDQSS score ranging 70 -100 belonged to grade I (mild) ; 101 -150 to grade II (moderate) ; >150 to grade III (severe). The correlation between the severity of GDQSS and TSH level was an- alyzed using Pearson and Partial correlation analyses. Results Levels of TSH, testosterone (T) , pro- lactin (PRL) were the lowest in grade I GDQSS patients, and they were the highest in grade lIl GDQSS patients (P <0. 01). Pearson correlation analysis showed that GDQSS score was positively correlated with TSH level (r =0. 676, P <0. 01). They were still positively correlated by using Partial correlation after controlling body mass index (BMI) , waist hip ratio (WHR) , homeostasis model of assessment-insulin resistance (HOMR-IR) factors (r =0. 663, P <0. 01). Conclusion Adolescent PCOS patients with obvi- ous GDQSS symptoms might be associated with increased TSH level.

Treatment of irreducible atlantoaxial dislocation using the transoral atlantoaxial pedicle screw technique. A report of 10 cases.

OBJECTIVE: The purpose of this work is to evaluate the outcome of the transoral atlantoaxial pedicle screw technique for the treatment of irreducible atlantoaxial dislocation (IAAD). PATIENTS AND METHODS: A total of 10 patients with IAAD were treated using the transoral atlantoaxial pedicle screw technique. We compared preoperative and postoperative JOA (Japanese Orthopedic Association) scores and observed bone graft fusion rate of the atlantoaxial joint, and examined whether our technique was suitable for the treatment of IAAD. RESULTS: The mean preoperative and postoperative JOA scores (9.2 ± 0.63 and 12.9 ± 0.73, respectively) were significantly different (P < 0.05). The atlantoaxial rigid bony fusion rate was 100 % in 10 cases. All cases were followed up for an average of 5.1 years (range 3.5-6 years). CONCLUSION: The transoral atlantoaxial screw reconstruction plate technique is a novel surgical technique for the treatment of IAAD in upper cervical diseases.

Anterior pedicle screw fixation of C2: an anatomic analysis of axis morphology and simulated surgical fixation.

STUDY DESIGN: Human cadaveric study measuring the morphology of C2 vertebra, description of anterior placement of pedicle screw with post-fixation computed tomography (CT) analysis. OBJECTIVE: To assess the potential feasibility and safety anterior placement of C2 pedicle screws. SUMMARY OF BACKGROUND DATA: Posterior pedicle screw fixation has become an established technique for upper cervical reconstruction. To our knowledge few reports in the previous literature have described the placement of or anatomy related to anteriorly approach C2 pedicle screws. METHODS: The morphology of 60 human C2 vertebrae was measured directly to assess the size, position, and relative approach angle of the pedicles from an anterior perspective. In an additional 20 cadaveric cervical spines, bilateral 3.5 mm titanium C2 pedicle screws were placed and analyzed for pedicle morphology and placement accuracy with thin cut, 1 mm axial CT. RESULTS: The mean C2 pedicle width measured directly and by CT scan was 7.8 and 6.6 mm, and the average length of the right and left pedicle was 26.4 and 25 mm, respectively. The mean transverse angle (α) was 17.6° and 21.4°, whereas declination angle (ß) anterior to posterior was 13.8° and 10.6°, respectively. CONCLUSIONS: Quantitative data regarding C2 pedicle shape and location with respect to the anterior placement of pedicle screws have not been previously reported. This study indicates that anterior placement of 3.5 mm C2 pedicle screws through a transoral approach may be both feasible and safe and also provides an important anatomic analysis that may guide clinical application.