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// Zongwei Lin 1,* , Shao Qian 3,* , Yan Gong 2,* , Jianwei Ren 6 , Lixia Zhao 4 , Dongxiao Wang 5 , Xiaowei Wang 1 , Yun Zhang 1 , Zhe Wang 2 and Qunye Zhang 1 1 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, and The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China 2 Division of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China 3 Department of Women Health Care, Jinan Maternity and Child Care Hospital, Jinan, China 4 Pharmacy Department of Shandong Medical College, Jinan, China 5 Department of Pharmacy, Chinese PLA General Hospital, Beijing, China 6 Health Division of Guard Bureau, General Staff Department of Chinese PLA, Beijing, China * These authors have equally contributed to this study Correspondence to: Qunye Zhang, email: // Zhe Wang, email: // Keywords : T cell receptor β, atherosclerosis, immune repertoire, next-generation DNA sequencing, complement determining region 3, Immunology and Microbiology Section, Immune response, Immunity Received : April 12, 2017 Accepted : June 18, 2017 Published : August 03, 2017 Abstract The T cell receptor (TCR) β repertoire directly reflects the status of T cell function. Meanwhile, the immune/inflammatory responses regulated by T cells are the critical determinants of atherosclerosis development. However, due to technical limitations, the composition and molecular characteristics of the TCR repertoire in atherosclerotic patients have not been fully elucidated. In the present study, we use powerful immune repertoire sequencing technology to study this issue. Results show that the utilization of V and/or J genes and the diversity of TCRβ repertoire in atherosclerotic plaques are significantly reduced compared to those in the peripheral blood of normal subjects and atherosclerotic patients. The frequencies of the common T cell clones with certain lengths of the complement determining region 3 regions are notably different among all groups. The high-frequency common clones are also increased in the atherosclerotic plaques compared to that in the other two groups. The expansion of several T cell clonotypes (V29-1J2-1, V20-1J1-6, V6-3J2-7 and V11-2J2-2) is validated in atherosclerotic patients. In short, this study reveals that the diversity of TCR β repertoire significantly decreases in atherosclerotic plaques, probably because of the reduced utilization of VJ genes and marked expansion of some T cell subclones. It provides the basis for understanding the roles of T lymphocytes in the pathogenesis of atherosclerosis.

Histone deacetylase inhibitors (HDACi) are a promising therapeutic intervention for stroke. The involvement of the anti-inflammatory effects of HDACi in their neuroprotection has been reported, but the underlying mechanisms are still uncertain. Given the post-stroke inflammation is a time-dependent process, starting with acute and intense inflammation, and followed by a prolonged and mild one, we proposed whether target the early inflammatory response could achieve the neuroprotection of HDACi? To test this hypothesis, a single dose of suberoylanilide hydroxamic acid (SAHA) (50 mg/kg), a pan HDACi, was intraperitoneally (i.p.) injected immediately or 12 h after ischemia onset in a transient middle cerebral artery occlusion (tMCAO) mouse model. Compared with delayed injection, immediate SAHA treatment provided more protection, evidenced by smaller infarction volume, and a better outcome. This protection was accompanied by suppression of pro-inflammatory cytokines and reduction of activated microglia in the early stage of post-stroke inflammation. Moreover, SAHA treatment suppressed M1 cytokine expression (IL-6, TNF-α, and iNOS) while promoted the transcription of M2 cytokines (Arg-1 and IL-10) in LPS-challenged mouse microglia, and enhanced CD206 (M2 marker) but decreased CD86 (M1 markers) levels in microglia isolated from the ipsilateral hemisphere of MCAO mice. Collectively, our data suggested that the protection of SAHA on ischemic brain injury was closely associated with its inhibition on the early inflammatory response, and this inhibition was related to its reducing microglia activation and priming the activated microglia toward a more protective phenotype.

Astaxanthin is a natural product gaining increasing attention due to its safety and anti-cancer properties. In this study, we investigated the mechanisms of the anti-cancer effects of astaxanthin on prostate cancer (PCa) cell lines using aggressive PCa DU145 cells. Also an instantaneous silenced cell line (si-STAT3) derived from DU145 and a control cell line (si-NK) were used for the MTT and colony formation assays to determine the role of astaxanthin in proliferation and colony formation abilities. Flow cytometry assays were used to detect the apoptosis of tumor cells. Migration and invasion assays detected the weakening of the respective abilities. Western blot and RT-PCR tests detected the levels of STAT3 protein and mRNA. Astaxanthin resulted in suppression of the proliferation of DU145 cells and the level of STAT3. The treatment of DU145 cells with astaxanthin decreased the cloning ability, increased the apoptosis percentage and weakened the abilities of migration and invasion of the cells. Furthermore, astaxanthin reduced the expression of STAT3 at protein and mRNA levels. The effects were enhanced when astaxanthin and si-STAT3 were combined. The results of animal experiments were consistent with the results in cells. Thus, astaxanthin inhibits the proliferation of DU145 cells by reducing the expression of STAT3.

The flexion–relaxation phenomenon (FRP) in back muscles is related to the lower back load. Although the FRP has been widely discussed, the effect of wearing jeans—a common attire in workplaces—on the FRP is unexplored. This study recruited 20 male participants with high and low flexibilities (10 each) and measured the related muscle activity and lumbopelvic movement at five trunk flexion angles (0°–90°) when wearing two types of bottom wears (swim trunks and fit jeans). Results revealed that the bottom wear type and trunk angle significantly affected all responses, whereas flexibility affected only erector spinae and hamstring activities. Participants with high flexibility and wearing swim trunks exhibited greater erector spinae activity than did those with low flexibility and wearing jeans. Thus, those who have low flexibility or are wearing jeans are likely to experience more activity reductions in erector spinae. However, the result with hamstring activity was the opposite. Wearing jeans limited participants’ pelvic rotation, forcing them to bend their lumbar spine further to complete trunk flexion, thus reducing erector spinae activity. A looser attire should be chosen to avoid constraining the pelvic rotation when work involves a deep trunk flexion. Relevance to industry People wearing jeans have limited pelvic movement and decreased erector spinae activity during deep trunk flexion, and this may further strain their interspinous ligaments. Thus, people should not wear fit jeans when in workplaces where their work involves stooping or trunk flexion exceeding 45° to minimize the load on their lower back.

This study is aimed to investigate the role of microRNA-144 (miR-144) in osteosarcoma cell line F5M2 proliferation, apoptosis, invasion, and metastasis. Between 2007 and 2014, 66 cases of osteosarcoma samples in the corresponding adjacent normal tissue samples were selected from surgical resection or biopsy in the Department of Orthopedics, Shengjing Hospital, China Medical University. MiR-144 levels and Ezrin messenger RNA (mRNA) levels in osteosarcoma and the adjacent bone tissues were detected, and clinical and pathological features were analyzed. Exogenous miR-144 was transfected into human osteosarcoma cell lines at two different concentrations (low and high), and the expression levels of miR-144 and Ezrin protein between highly metastatic osteosarcoma cells and lowly metastatic osteosarcoma cells were compared. Real-time polymerase chain reaction (RT-PCR) and Western blot were used for detecting the expression levels of miR-144 or Ezrin protein, respectively. Cell proliferation was measured by methylthiazol tetrazolium (MTT) assay. Cell invasion and migration was evaluated by Transwell assays. Finally, flow cytometry was employed to determine the cell apoptosis. MiR-144 expression in osteosarcoma tissue was significantly lower than that in the surrounding normal bone tissue (P

In this study, we aim to examine the association of microRNA-586 (miR-586) with osteosarcoma (OS) cell proliferation, apoptosis, invasion, and metastasis. U2-OS cell lines were divided into 4 groups: an miR-586 group, anti-miR-586 group, control group (empty plasmid) and blank group (no plasmid). qRT-PCR was used to detect miR-586 expression, cell counting kit-8 and EdU assays to detect cell proliferation, flow cytometry to detect cell cycle distribution, Annexin V/PI double staining to detect cell apoptosis, and the Transwell assay to detect cell invasion and metastasis. miR-586 expression was significantly higher in the miR-586 group but significantly lower in the anti-miR-586 group compared with the control and blank groups. Cell proliferation at 2-5 days after cell transfection and the EdU-positive cell number increased obviously in the miR-586 group but decreased clearly in the anti-miR-586 group. In the miR-586 group, cells at G0/G1 stage and apoptosis cells significantly decreased, while cells at G2/M and S stages and invasive and metastatic cells significantly increased compared to the control and blank groups; however, opposite trends were found in the anti-miR-586 group. Downregulation of miR-586 expression in OS may inhibit cell proliferation, invasion and metastasis, and promote cell apoptosis.

The emergence of electricity transmission with farther transporting distance, extra-higher voltage and greater transporting power and the formation of the regional interconnected power grid have greatly increased the probability of blackout, this phenomenon has fully exposed the vulnerability of large-scale interconnected power systems. In this paper, Electrical betweenness based on load transfer coefficient is proposed to construct structural vulnerability assessment index. Meanwhile, it is verified that the method is rational and available by analysising the difference of the IEEE-39 system between three attack modes.

Hesperidin (HDN) is a citrus bioflavonoid, which widely exists in many plants. Previous researches have proved that HDN has several functions such as anti-oxidant, anti-tumor, anti-inflammatory, immune regulation and so on. In the present study, we explored the protective effects of HDN on concanavalin A (Con A)-induced hepatic injury. Acute hepatic injury model was established successfully by intravenous administration of Con A (15 mg/kg) in male C57BL/6 mice, and HDN was pretreated for 10 days before Con A challenge. It was found that the hepatic injury was notably improved in HDN pretreated mice. Furthermore, hepatic oxidative stress and the production of proinflammatory cytokines including TNF-α and IFN-γ were decreased by HDN pretreatment. More importantly, compared with Con A-treated mice, the expression and releasing of HMGB1 and T-cell activation were markedly reduced in HDN pretreated mice. Thus, these results suggest that HDN protects mice from Con A-induced hepatic injury by suppressing hepatocyte oxidative stress, producing cytokines, expressing and releasing HMGB1 and activating T cells.

Ovarian cancer remains a challenging disease for which improved treatments are urgently needed. Tim-3 acts as a negative regulatory molecule and plays a critical role in immune tolerance. In the current study, we investigated the expression of Tim-3 on peripheral CD4+ T and CD8+ T cells in ovarian cancer. A total of 52 ovarian cancer patients and 56 healthy controls were recruited and leukocytes from peripheral blood mononuclear cells were analyzed for Tim-3 surface expression by flow cytometry. Data showed that expression of Tim-3 was significantly increased in both CD4+ and CD8+ T cells in ovarian cancer cases than in controls (p

Background The purpose of this study was to investigate saliva cortisol levels of Chinese patients with discogenic sciatica and to clarify the relationship between psychosocial factors and saliva cortisol levels. We also intended to elucidate the effect of different types of cortisol secretion on the prognosis of lumbar discectomy.

Objective To evaluate the feasibility, safety and efficacy of atlas pedicle screws system fixation and fusion for the treatment of upper cervical diseases. Methods Twenty-three consecutive patients with upper cervical disorders requiring stabilization, including 19 cases of atlantoaxial dislocation (4 congenital odontoid disconnections, 6 old odontoid fractures, 4 fresh odontoid fractures of Aderson II C, 3 ruptures of the C1 transverse ligament, and 2 fractures of C1), 2 cases of C2 tumor (instability after the resection of the tumors), and 2 giant neurilemomas of C2-C3(instabilityafter resectionofthetumors), weretreated by posterior fixation and fusion with the atlas pedicle screw system, in which the screws were inserted through the posterior arch of C1. The operative time, bleeding volume and complications were reported. All patients were immobilized without external fixation or with rigid cervical collars for 1-3 months. All patients were followed up and evaluated with radiographs and CT. Results In the 23 patients, 46 C1 pedicle screws, 42 C2 pedicle screws and 6 lower cervical lateral mass screws and 2 lower cervical pedicle screws were placed. The mean operative time and bleeding volume was 2.7 hours and 490 ml respectively. No intraoperative complications were directly related to surgical technique. No neurological, vascular or infective complications were encountered. All patients were followed up for 3-36 months (average 15 months). Firm bony fusion was documented in all patients after 3-6 months. One patient with atlas fracture showed anterior occipitocervical fusion. There was no implant failure. Conclusions Posterior fixation and fusion of the atlas pedicle screw system is feasible and safe for the treatment of upper cervical diseases, and may be applicable to a larger number of patients.

Flupentixol and an internal standard, loperamide were extracted from human plasma by liquid–liquid extraction and analyzed on a Thermo Hypersil HyPURITY C18 column, with 10 mM ammonium acetate–acetonitrile–methanol (26:62:12, v/v/v) as mobile phase, coupled with electrospray ionization mass spectrometry (ESI–MS). The protonated analyte was quantified by selected-ion monitoring (SIM) with a quadrupole mass spectrometer in a positive-ion mode. The calibration curve was linear (r = 0.9990) over the concentration range: 0.039–2.5 ng mL−1. Intra-day and inter-day precision (RSD%) were less than 13.05%. The established method was successfully applied for the determination of pharmacokinetics of flupentixol in human plasma.

STUDY DESIGN Anatomical measurements and in vitro biomechanical testing were performed to evaluate a new method for posterior C1 fixation. OBJECTIVE This study sought to assess C1 posterior arch crossing screw fixation for posterior C1-C2 fixation, using anatomical measurements and biomechanical testing with traditional C1 pedicle screws (PS) in a cadaveric model. SUMMARY OF BACKGROUND DATA Atlantoaxial instability often requires surgery, and the current methods for atlas fixation incur some risk to the vascular and neurological tissues. Thus, new, effective, and safe methods are needed for salvage operations. METHODS Morphometric analysis of the C1 posterior arch was performed using 3-dimensional computed tomography. Six fresh ligamentous human cervical spines (C0-C4) were evaluated for their biomechanics. The specimens were tested in their intact condition and after stabilization (C1-C2 PS, C1 posterior arch screws [PAS] with C2 PS) and injury due to 1.5 N·m of pure moment in flexion, extension, lateral bending, and axial rotation. During testing, 3-dimensional angular motion was measured with a motion capture platform (Vicon Nexus). Data for all scenarios were recorded, and statistical analysis was performed. RESULTS Anatomical assessment indicated that 91.51% of C1 posterior tubercles exceeded 7 mm in thickness, 93.40% had a width of the posterior arch of greater than 3.5 mm, and 65.57% had a unilateral screw length of greater than 15 mm, indicating that the posterior arch fixation could be achieved by two 3.5 × 15-mm screws placed in a crossed manner. Twenty-two cases (11%) were not suitable for crossing screw placement because the posterior arch was flat and the entry point was present on the same side. Biomechanical testing showed that the PS and PAS rod-screw systems significantly reduced flexibility in flexion, extension, and rotation compared with the intact position. For lateral bending, there was a trend for the C1 PS and PAS systems toward decreased flexibility in comparison with the intact position. At the same time, C1 PAS decreased C1-C2 movement by 33.0% in left bending (P = 0.171) and 24.4% in right bending (P = 0.095); however, no significant difference was observed for left bending with C1 PAS compared with C1 PS, and the C1 PS and PAS systems significantly reduced the flexibility more than destabilization. CONCLUSION Crossing screw fixation of the C1 posterior arch is straightforward and imposes little risk of injury to the neural and vascular structures as long as the implants remain intraosseous. According to the results of our anatomical and biomechanical study, C1 posterior arch crossing screw fixation may constitute an alternative method for posterior atlantoaxial fixation. LEVEL OF EVIDENCE 3.