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Non-human primates are most suitable for generating cervical experimental models, and it is necessary to study the anatomy of the cervical spine in non-human primates when generating the models. The purpose of this study was to provide the anatomical parameters of the cervical spine and spinal cord in long-tailed macaques (Macaca fascicularis) as a basis for cervical spine-related experimental studies. Cervical spine specimens from 8 male adult subjects were scanned by micro-computed tomography, and an additional 10 live male subjects were scanned by magnetic resonance imaging. The measurements and parameters from them were compared to those of 12 male adult human subjects. Additionally, 10 live male subjects were scanned by magnetic resonance imaging, and the width and depth of the spinal cord and spinal canal and the thickness of the anterior and posterior cerebrospinal fluid were measured and compared to the relevant parameters of 10 male adult human subjects. The tendency of cervical parameters to change with segmental changes was similar between species. The vertebral body, spinal canal, and spinal cord were significantly flatter in the human subjects than in the long-tailed macaques. The cerebrospinal fluid space in the long-tailed macaques was smaller than that in the human subjects. The anatomical features of the cervical vertebrae of long-tailed macaques provide a reference for establishing a preclinical model of cervical spinal cord injury.

Increasing evidence has confirmed the vital roles of circular RNAs (CircRNAs) in the drug resistance of breast cancer (BC). Herein, we intended to study the effect of circular RNA FAT atypical cadherin 1 (circFAT1) on BC oxaliplatin (OX) resistance and find out the potential molecular mechanism in it. In this study, mRNA and protein levels of genes were measured by RT-qPCR and western blotting, respectively. Luciferase reporter assay confirmed the relationship between microRNA-525-5p (miR-525-5p) and circFAT1 or spindle and kinetochore-associated complex subunit 1 (SKA1). CCK-8, transwell, and flow cytometry experiments were utilized to investigate the chemosensitivity, migration, invasion, and apoptosis of BC cells. Gene Set Enrichment Analysis (GSEA) was applied to discover possible pathways related to SKA1. It was uncovered that circFAT1 was overexpressed in OX-resistant BC tissues and cells. Functional experiments showed that circFAT1 depletion reduced the level of chemoresistance-related genes. Moreover, circFAT1 knockdown remarkably facilitated apoptosis and decreased OX (half-maximal inhibitory concentration) IC50 value, migration, and invasion in OX-resistant BC cells. It was identified that miR-525-5p directly targeted circFAT1 and SKA1. Besides, rescue assays exhibited that circFAT1 promoted OX resistance in BC cells via the miR-525-5p/SKA1 regulatory network. Furthermore, GSEA and western blotting identified that SKA1 activated the Notch and Wnt pathway in OX-resistant BC cells. In conclusion, our results demonstrated that circFAT1 conferred OX resistance in BC by regulating the miR-525-5p/SKA1 via the Notch and Wnt pathway, providing a potential therapeutic target for patients with OX-resistant BC., Graphical Abstract

Background Macrophages are key innate immune cells implicated in the pathogenesis of Behçet’s disease (BD), and macrophage polarization plays a pivotal role in inflammatory response. This study aimed to investigate the role of BD serum on the phenotypes and functions of macrophage polarization. Methods BD or HC serum-treated human monocyte-derived macrophages (HMDMs) were examined M1/M2 phenotypes using flow cytometry and ELISA. The phagocytic capacity of HMDMs and CD4+T cell differentiation facilitated by HMDMs were measured by flow cytometry. Transcriptome analysis of BD and HC serum-stimulated HMDMs was conducted to identify differentially expressed genes. NF-κB signaling was examined using western blot to explore the mechanism of macrophage polarization induced by BD serum. Results BD serum-treated macrophages expressed a higher level of CD86, IL-12, and TNF-α and a lower level of CD163, which were compatible with the M1-like phenotype. Furthermore, BD serum-treated macrophages showed enhanced phagocytic capacity and promoted more Th1 cell differentiation. Sixty-one differentially expressed genes were identified between BD and HC serum-treated macrophages and were enriched in NF-κB signaling. BD serum-treated macrophages showed upregulated p-p65 and downregulated IκBα, and NF-κB inhibitor attenuated BD serum-stimulated M1-like phenotype. Conclusions BD serum promoted macrophage polarization toward a proinflammatory M1-like phenotype through NF-κB signaling and potentially facilitated inflammation in BD. M1 polarized macrophages may be a potential therapeutic target for BD.

The aim was to investigate the effectiveness of colour duplex ultrasound (CDU) plus contrast enhanced ultrasound (CEUS) vs. computed tomography angiography (CTA) for surveillance in patients with isolated mesenteric artery dissection (IMAD).Patients who underwent CDU, CEUS, and CTA for surveillance of IMAD between January 2012 and May 2019 were included in the study. The accuracy of CDU, CEUS, and CTA for determining the morphological characteristics of IMAD was analysed.A total of 42 patients undergoing 76 total imaging examinations during follow up were included. Both CTA and CDU plus CEUS demonstrated the thrombosed false lumen for 28 (36.8%) examinations and the dissecting aneurysm for 20 (26.3%) examinations (both κ = 1.0). The diameter of the dissecting aneurysm was 5.03 ± 1.25 mm using CDU and CEUS vs. 5.27 ± 1.23 mm on CTA (coefficient of consistency, 0.997; p .001). The entry points were visualised by CDU and CEUS for 20 (26.3%) examinations and by CTA for 14 (18.4%) examinations (κ = 0.769); no re-entry points were visualised by CDU and CEUS for any examinations but re-entry points were visualised by CTA for two (2.6%) examinations. The minimum inner diameter was 2.80 ± 1.30 mm on CDU and CEUS vs. 2.52 ± 1.29 mm on CTA (coefficient of consistency, 0.999; p .001). The peak systolic velocities were 128.2 ± 13.0 cm/s at diagnosis and 98.7 ± 4.9 cm/s after one month (p .001).The combination of CDU and CEUS can be used in place of CTA for the surveillance of IMAD.

Background Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune inflammatory disease predominantly found in women of child-bearing age. Neurogenic pulmonary edema (NPE) is a recalcitrant complication that occurs after injury to the central nervous system and has an acute onset and rapid progression. Limbic encephalitis is an inflammatory encephalopathy caused by viruses, immune responses, or other factors involving the limbic system. NPE caused by SLE is rare. Case presentation Here, we report a case of a 21-year-old woman with SLE who experienced five episodes of generalized tonic–clonic seizure after headache and dyspnea. Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) 2 antibody was tested positive in the serum and cerebrospinal fluid. Electrocardiography (EEG) indicated paroxysmal or sporadic medium amplitude theta activity. In addition, chest computed tomography (CT) showed multiple diffuse consolidations and ground-glass opacities. We finally considered a diagnosis of NPE and AMPAR limbic encephalitis. The patient's symptoms improved obviously after methylprednisolone pulse therapy and antiepileptic treatment. Conclusions NPE can be a complication of neuropsychiatric lupus erythematosus (NPSLE). AMPAR2 antibodies may be produced in NPSLE patients, especially in those with high polyclonal IgG antibody titers. More basic and clinical studies are required to confirm these observations and elucidate the pathogenicity of encephalitis-related autoantibodies in SLE patients.

Systemic vasculitis is a heterogeneous group of multisystem autoimmune disorders characterized by inflammation of blood vessels. Although many progresses in diagnosis and immunotherapies have been achieved over the past decades, there are still many unanswered questions about vasculitis from pathological understanding to more advanced therapeutics. Extracellular vesicles (EVs) are double-layer phospholipid membrane vesicles harboring various cargoes. EVs can be classified into exosomes, microvesicles (MVs), and apoptotic bodies depending on their size and origin of cellular compartment. EVs can be released by almost all cell types and may be involved in physical and pathological processes including, inflammation and autoimmune responses. In systemic vasculitis, EVs may have pathogenic involvement in inflammation, autoimmune responses, thrombosis, endothelium injury, angiogenesis and intimal hyperplasia. EV-associated redox reaction may also be involved in vasculitis pathogenesis by inducing inflammation, endothelial injury and thrombosis. Additionally, EVs may serve as specific biomarkers for diagnosis or monitoring of disease activity and therapeutic efficacy, i.e. AAV-associated renal involvement. In this review, we have discussed the recent advances of EVs, especially their roles in pathogenesis and clinical involvements in vasculitis.

Systemic vasculitis is diverse group of autoimmune disorders which are characterized by inflammation of blood vessel walls with deep aching and burning pain. Their underlying etiology and pathophysiology still remain poorly understood. Extracellular vesicles (EVs), including exosomes, microvesicles (MVs), and apoptotic bodies, are membrane vesicular structures that are released either during cell activation, or when cells undergo programmed cell death, including apoptosis, necroptosis, and pyroptosis. Although EVs were thought as cell dusts, but now they have been found to be potently active since they harbor bioactive molecules, such as proteins, lipids, nucleic acids, or multi-molecular complexes. EVs can serve as novel mediators for cell-to-cell communications by delivery bioactive molecules from their parental cells to the recipient cells. Earlier studies mainly focused on MVs budding from membrane surface. Recent studies demonstrated that EVs may also carry molecules from cytoplasm or even from nucleus of their parental cells, and these EVs may carry autoantigens and are important in vasculitis. EVs may play important roles in vasculitis through their potential pathogenic involvements in inflammation, autoimmune responses, procoagulation, endothelial dysfunction/damage, angiogenesis, and intimal hyperplasia. EVs have also been used as specific biomarkers for diagnostic use or disease severity monitoring. In this review, we have focused on the aspects of EV biology most relevant to the pathogenesis of vasculitis, discussed their perspective insights, and summarized the exist literature on EV relevant studies in vasculitis, therefore provides an integration of current knowledge regarding the novel role of EVs in systemic vasculitis.

STUDY DESIGN Retrospective analysis of computed tomographic images of 92 normal pediatric cervical vertebrae. OBJECTIVE The aim of this study was to ascertain the feasibility of the pedicle, intralaminar, and lateral mass screws fixation in children. SUMMARY OF BACKGROUND DATA Fixation techniques of C7 vertebrae are technically challenging in the pediatric population. Although the techniques offer alternatives to screws placement at C7 spine in adult, there is no consensus to apply these screws in children. METHODS A total of 92 patients (59 males and 33 females) from 3- to 16-year old divided into three groups (group 1, 1-6 years; group2, 7-10 years; group 3, 11-16 years) were included. Measurements were taken through computed tomography (CT) imaging without evidence of spinal trauma. Length, width, and angle of lamina and pedicle were measured, and lateral mass length was also assessed. RESULTS There was no statistical difference between the left and right sides, as well as the sexes. In 1 to 6 years' age group, 83.3% of the laminas and 87.5% of the pedicles measured have thicknesses of >3.5 mm. In 7 to 10 years' age group, 84.0% of the laminas and all the pedicles observed have thicknesses of >3.5 mm. In 11 to 16 years' age group, 88.4% of the laminas and 97.7% of the pedicles measured have thicknesses of >3.5 mm. Most of the spinolaminar angles were between 42.5° and 56°. There are three cases (3.3%) having lateral mass length >12 mm. CONCLUSION It is feasible to insert a screw (O 3.5 mm) in C7 lamina in children, and the intralaminar screw fixation is a safe and reliable technique. Around 49°, the spinolaminar angle with axial position, can be used as reference for placing screws in the C7 lamina. Preoperative CT scan will help surgeons to insert the laminar screw safely and accurately. LEVEL OF EVIDENCE N/A.

Behcet's disease (BD) patients have abnormal FcγR polymorphisms, the implication of which remains elusive. We examined FcγRIIb expression on neutrophils, monocytes, B cells, natural killer cells, dendritic cells and T cells, and FcγRI and FcγRIII expression on monocytes in BD patients and healthy controls using flow cytometry. We further stimulated monocytes with IgG and (or) lipopolysaccharide (LPS) and measured IL-6 and TNF-α production by enzyme-linked immunosorbent assay. We found that BD monocytes expressed a lower level of FcγRIIb and a higher level of FcγRIII, which were correlated with erythrocyte sedimentation rate and C-reactive protein and were rescued after treatment. Furthermore, LPS- and IgG-stimulated BD monocytes produced higher levels of IL-6 and TNF-α than HC monocytes. In summary, we found that BD monocytes downregulated FcγRIIb expression and upregulated FcγRIII expression, which were correlated with disease activity and potentially contributed to monocyte hyperactivation in BD.

Dihydroartemisinin (DHA), an active metabolite and derivative of artemisinin, is the most effective antimalarial drug and has strong antitumor activity in various tumor types. It has recently been reported that DHA can induce autophagy and has significant effects on multiple myeloma (MM), but the mechanisms and the relationship between the autophagy and apoptosis induced by DHA remain to be elucidated. Herein, we demonstrated that DHA significantly induces cell death in a dose- and time-dependent manner via the extrinsic and intrinsic apoptosis pathways. Moreover, DHA-induced autophagy, which plays a prodeath role in MM, can regulate canonical apoptosis and vice versa. Furthermore, the P38/MAPK signaling pathway is responsible for decreased autophagy and increased apoptosis. DHA induces autophagy and apoptosis also through the inhibition of the Wnt/β-catenin signaling pathway. In addition, DHA shows a strong effect in a xenograft mouse model. Collectively, these findings reveal that DHA, as an artemisinin-based drug, could be an effective and safe therapeutic agent for MM.

Background Conclusions regarding the association between antithyroid antibodies or thyroid dysfunction and rapid cycling bipolar disorder (RCBD) have been conflicting. Previous studies suggest that the impact of antithyroid antibodies on mental wellbeing seems to be independent of thyroid function. Here, we investigated their independent association with RCBD in a large, well-defined population of bipolar disorder (BD). Methods Fast serum levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid Stimulating Hormone (TSH), TPO-abs and Tg-abs were simultaneously measured in 352 patients with BD. Clinical features of BD were collected through semi-structural interview conducted by trained interviewers with background of psychiatric education. Results Neither hypothyroidism nor hyperthyroidism was significantly associated with RCBD. Both TPO-abs and Tg-abs were significantly related to RCBD, even after controlling for gender, age, marriage status, education, antidepressants treatment, comorbidity of thyroid diseases, and thyroid function (serum levels of FT3, FT4 and TSH). Although TPO-abs and Tg-abs were highly correlated with each other, binary logistic regression with forward LR selected TPO-abs, instead of Tg-abs, to be associated with RCBD. TPO-abs was significantly, independently of Tg-abs, associated with hyperthyroidism, while Tg-abs was marginally significantly related to hypothyroidism at the presence of TPO-abs. Conclusion TPO-abs might be treated as a biomarker of RCBD. Further exploring the underlying mechanism might help understand the nature of RCBD and find out new treatment target for it.

ObjectivesTo survey anxiety and depression symptoms to COVID-19 outbreak in the public, medical staff and patients during the initial phase of the pandemic.DesignCross-sectional online survey administered through WeChat Mini Program using Chinese versions of Zung Self-rating Depression Scale and Zung Self-rating Anxiety Scale.SettingGuangzhou, China.Participants47 378 public, 1512 medical staff and 125 patients with COVID-19.ResultsHigher rates of depression (47.8%) and anxiety symptoms (48.7%) were shown by patients who were screened positive compared with those of the public (35.6%, 25.7%) or medical staff (15.4%, 13.3%). The professional identity of a nurse, conditions of ‘with an infected family member’ and ‘working at the frontline’ were risk factors to depression or anxiety symptoms for the medical staff. Younger age, lower educational level, female and not having adequate masks were the risk factors for the public.ConclusionThe COVID-19 outbreak increased people’s depression or anxiety emotion responses, which varied extensively among the patients, public and medical staff.

To investigate the clinical characteristics of Bechet's disease (BD) with respect to gender and age in China.Clinical data of 489 BD patients admitted to Peking Union Medical College Hospital (PUMCH) and registered by the BD registry database established by PUMCH from March 2014 to January 2019 were collected and analyzed in this study. Demographics, medical histories, clinical manifestations, laboratory test results, imaging findings, assessment of disease activity, treatment regimen, as well as the outcomes were reviewed.A total of 489 BD patients were included in this study, among them 286 males (58.5%) and 203 females (41.5%) with a male-to-female ratio of 1.41 and a median age of 34 years (interquartile range 28-44 years old). The results revealed that ocular lesions (P = 0.005), vascular lesions(P 0.001), pseudofolliculitis (P 0.001), and positive pathergy test (P = 0.002) were more commonly found in males, while genital ulceration was more prevalent in females (P 0.001). Vascular lesions (P = 0.024) and gastrointestinal ulcers (P = 0.010) were more common in BD patients after the age of 40, while pseudofolliculitis was more common in patients under the age of 40 (P = 0.004) and ocular lesions (P = 0.017) occurred mainly in patients under the age of 35. Male predominance of ocular involvement was more apparent in their third decades (PThe clinical characteristics of BD were different with respect to gender and age. Key Points • Ocular and vascular lesions, pseudofolliculitis, and positive pathergy test were more common in male BD patients. • Genital ulceration showed female predominance in BD patients. • Vascular lesions and gastrointestinal ulcers were more common in older BD patients. • Pseudofolliculitis and ocular lesions occurred mainly in younger BD patients.

Background To investigate the diagnostic value of the interferon-γ release assay (IGRA) for detecting tuberculosis (TB) infection in patients with Behçet’s disease (BD). Methods We retrospective analyzed the data collected from 173 BD patients hospitalized between 2010 and 2015. Ninety-nine healthy volunteers were enrolled as a control group. IGRA was performed using T-SPOT.TB. The diagnosis of active TB (ATB) was based on clinical, radiological, microbiological, histopathological information and the response to anti-TB therapy. Latent TB (LTB) infection was defined as asymptomatic patients with positive T-SPOT.TB. Results TB infection was documented in 59 BD patients (34.1%). The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of T-SPOT.TB for the diagnosis of ATB were 88.9%, 74.8%, 29.1%, 98.3%, 3.53 and 0.15, respectively. The receiver-operating-characteristic curve demonstrated that spot-forming cells (SFCs) of 70/106 PBMC was the optimal cutoff for diagnosing ATB, with an area under the curve of 0.891. Furthermore, the median SFCs in ATB group was significantly higher than those in LTB infection (466/106 PBMC vs. 68/106 PBMC, p = 0.007) or previous TB infection (466/106 PBMC vs. 96/106 PBMC, p = 0.018). A significant discrepancy between T-SPOT.TB and tuberculin skin test was noted (kappa coefficient = 0.391, p = 0.002). Conclusions T-SPOT.TB, an IGRA, may assist in the diagnosis of ATB in BD patients, and the higher SFCs suggest ATB in BD patients.

Objective. To investigate the clinical features and potential risk factors of aneurysmal lesions in Behcet’s disease (BD). Methods. We retrospectively reviewed the clinical data of BD patients with aneurysmal lesions in our institute from 1997 to 2017 and compared them with 207 BD patients without aneurysmal lesions. The treatment and outcome of these patients were also analyzed. Results. Sixty-nine patients were included with 117 aneurysmal lesions. The average period between BD onset and diagnosis of aneurysmal lesion was 5.4±5.5 years. Thirty-three patients (47.8%) had multiple aneurysmal lesions. Ten patients developed 20 pulmonary artery aneurysms alone. For the other 97 aortic and/or peripheral artery aneurysms in 59 patients, the most commonly affected vessels were abdominal aorta (27/97, 27.8%), coronary artery (10/97, 10.3%), and superficial femoral artery (8/97, 8.2%). Multivariate analysis revealed pathergy reaction (OR=3.78 (1.70-8.41)), arterial stenosis or occlusion (OR=44.12 (11.56-168.35)), and arterial thrombosis (OR=9.27 (2.33-36.93)) as independent predictors of aneurysmal lesions in BD. With a mean follow-up of 5.5±4.0 years, 40 patients (58.0%) achieved clinical improvements, 15 patients (21.7%) relapsed, and 10 patients (14.5%) died. The respective estimated cumulative 1- and 5-year relapse-free rates were 91.3% and 76.3%, and the respective estimated 1- and 5-year survival rates were 95.0% and 87.2%. Conclusion. Aneurysmal lesions are severe complications in BD. Pathergy reaction, arterial stenosis or occlusion, and arterial thrombosis are the risk factors of aneurysmal lesions in BD. Achieving BD remission and performing surgical or interventional procedures are both important in the treatment of these patients.

Purpose. Barium sulfate and lead oxide are commonly used for angiographic studies, but there is no report on the comparison of two contrast agents in angiography of cervical spinal cord. This study was aimed to compare the microvascular architecture of cervical spinal cord in rats after angiography with the barium sulfate agent to the lead oxide agent. Methods. Twelve adult Sprague-Dawley rats were randomly divided into the barium sulfate group (n=6) and the lead oxide group (n=6). Each rat was perfused under the same protocol using either two contrast agents. The angiography was evaluated with the vascular number at different ranks. The cervical spinal cord samples were scanned using micro-CT with low resolution and high resolution. The microvascular parameters, including ratio of vascular volume to tissue volume (VV/TV), vascular number (V.N), diameter (V.Dm), separation (V.Sp), connectivity density (Conn.D), structure model index (SMI), percentage, and volume of vessels at different diameters were measured. Results. The perfusion was better in the barium sulfate group, with more blood vessel trees of rank II and III visible compared to the lead oxide group. Low-resolution micro-CT analysis showed no difference in microvascular parameters except SMI between the two groups. High-resolution micro-CT analysis results showed that V.N and Conn.D of barium sulfate group were 60% and 290% more than those of the lead oxide group; however, V.Sp was 41% less than the lead oxide group. The percentage of vessels with diameter of 10 μm and 20 μm, and the volume of vessels with diameter of less than 100 μm was higher in the barium sulfate group than in the lead oxide group. The SMI index in the barium sulfate group was higher than that in the lead oxide group at both low resolution and high resolution. Conclusions. Compared with lead oxide, barium sulfate is more suitable for perfusion of cervical spinal cord microvessels, and cheap and nontoxic with high resolution.

Background Ventral defect caused by resection of the lesions involving the upper cervical spine commonly has been reconstructed with a fabricated mesh cage. Recently, a clival screw and plate fitted to the osseous anatomy of the craniovertebral junction was developed for this pathologic status. Objective To evaluate the stability a clivus plate system fixation (CPSF) for the craniovertebral junction and compare it with a conventional fashioned mesh cage fixation (FMCF). Methods Seven human fresh cadaveric specimens (occiput [Oc], atlas [C1], axis [C2], third cervical vertebra [C3], fourth cervical vertebra [C4]) were tested with intact and destabilization-reconstruction conditions. FMCF and CPSF were applied randomly to the clivus to the C3 segment combined with posterior occipitocervical fixation applied from the occiput to C4 segment, respectively. Specimens were subjected to a pure moment of 1.5 Nm in flexion, extension, lateral bending, and axial rotation, respectively. The range of motion (ROM) and neutral zone (NZ) from the occiput to C3 were calculated and compared between two anterior fixations. Results Motions were reduced significantly in all directions following FMCF and CPSF fixations when compared with the intact. The CPSF resulted in smaller ROM in lateral bending (0.3° vs. 0.6°, P = 0.015), axial rotation (0.6° vs. 1.2°, P = 0.023) and flexion (0.1° vs. 0.3°, P = 0.019), but similar ROM in extension (0.2° vs. 0.4°, P = 0.273) when compared with the FMCF. NZs with the CPSF were 0.1° in flexion-extension, 0.1° in lateral bending and 0.2° in axial rotation, respectively, and similar to NZs with the FMCF. Conclusions The clivus plate system fixation is biomechanically superior to the conventional fashioned mesh cage fixation in flexion, lateral bending and axial rotation, but equavalent in extension.

To explore the associated risk factors of symptomatic knee osteonecrosis (KON) in patients with systemic lupus erythematosus (SLE), we conducted a retrospective case–control study to compare the clinical and laboratory features between SLE patients with and without symptomatic KON matched by age and gender. Univariate and multivariate regression analyses were used to evaluate possible associated risk factors. Twenty (one male, nineteen females) out of 3941 lupus patients were identified as symptomatic KON, which was confirmed by magnetic resonance imaging. The mean age at KON onset was 34.4 (range 12–67) years, and the median course of lupus at KON onset was 72.5 (range 8–123) months. Univariate and multivariate analyses identified that the prevalence of cutaneous vasculitis (OR 5.23; 95 % CI 1.11–24.70), hyperfibrinogenemia (OR 4.75; 95 % CI 1.08–20.85), and elevated IgG levels (OR 6.05; 95 % CI 1.58–23.16) were statistically higher in KON group, and hydroxychloroquine (HCQ) usage was statistically lower in KON group (OR 0.27; 95 % CI 0.07–0.97). Glucocorticoid usage, in terms of maximal dose, duration of treatment, and the percentage of receiving methylprednisolone pulse therapy, did not show statistical difference between the two groups (p > 0.05). Symptomatic KON is a relatively rare complication of SLE. Cutaneous vasculitis, hyperfibrinogenemia, and elevated IgG levels are possible risk factors, whereas HCQ may provide a protective effect. Our results suggest that lupus activity as well as hypercoagulation status may play a role in the pathogenesis of KON in lupus.

Cognitive impairment is one of the core symptoms of schizophrenia, and patients with schizophrenia are at increased risk of metabolic syndrome (MS). However, the role of MS in cognitive impairment of schizophrenia is not established. This study investigated the correlation between neurocognitive, social cognitive performance and MS with schizophrenia. One hundred and fifty eight (158) schizophrenia patients were divided into 3 groups with ① normal metabolism, ② metabolic disorder (only meeting 1 or 2 MS criteria), and ③ metabolic syndrome (meeting 3 or more MS criteria). MATRICS Consensus Cognitive Battery)MCCB(and the Brief Psychiatric Rating Scale)BPRS(were used to evaluate cognitive performance and clinical symptoms. Blood samples were obtained to detect glucose and lipid metabolic levels. Overall MCCB and subscale T scores in the normal metabolism and metabolic disorder groups were better than in the MS group. After controlling for the confounding factors including age, sex, the usage of hypolipidemic and hypoglycemic drugs, and disease duration, metabolic deficits had effects on the symbol coding and spatial span scores. The results suggest that a defective metabolic state might play a role in neurocognitive performance of schizophrenia patients.

Variety of evidence suggests that low-grade inflammation may be involved in the pathophysiology of bipolar disorder (BD). However, the conclusion regarding the relationship between inflammation and BD has been inconsistent. In this study, we aimed to survey the prevalence of low-grade inflammation in a large Han Chinese population with BD and assess its impact on the clinical features of BD. 430 eligible cases were drawn from patients who were admitted or had ever been admitted for BD to the inpatient service of the psychiatric department of the Third Hospital of Sun Yat-sen University. Subjects with current active physical diseases or white blood count (WBC) >19.0 × 109/L (2 times the upper reference) were excluded. Serum C-reactive protein (CRP) levels and WBC were measured with fast blood sample. Low-grade inflammation was defined as CRP>3 mg/L or WBC > 9.5 × 109/L(the upper reference). Clinical features of BD were collected through semi-structural interview conducted by trained interviewers with background of psychiatric education. If defined as CRP>3 mg/L, the prevalence of low-grade inflammation among BD was 10.1% (41/404), it was positively associated with BMI (p = 0.012), comorbidity of glycolipid metabolic diseases(p = 0.018). After adjusting for BMI, it was found to be positively related to recent suicide attempt (p = 0.03), initiation with (hypo)manic episode(p = 0.047), leaden paralysis (p = 0.037) and family history of mental disorders(p = 0.012), while the association between comorbidity of glycolipid metabolic diseases and low-grade inflammation disappeared (p = 0.330). If defined as WBC > 9.5 × 109/L, the prevalence of low-grade inflammation was 8.1% (33/409), it was positively associated with psychotic features (p = 0.011) and adverse life events before the onset of illness(p A much lower prevalence of low-grade inflammation in BD is found among Han Chinese population than among western population. Low-grade inflammation of different definition impacts differentially on the clinical features of BD.

Background The diagnosis of Behçet’s disease (BD) remains challenging due to the lack of diagnostic biomarkers. This study aims to identify potential serum metabolites associated with BD and its disease activity. Methods Medical records and serum samples of 24 pretreated BD patients, 12 post-treated BD patients, and age-matched healthy controls (HC) were collected for metabolomics and lipidomics profiling using UPLC-QTOF-MS and UPLC-QTOF-MSE approaches. Additionally, serum samples from an independent cohort of BD patients, disease controls including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Takayasu’s arteritis (TA), Crohn’s disease (CD) patients, and HC were collected for further validation of two potential biomarkers using UPLC-QTOFMS analysis. Results Unsupervised principal component analysis (PCA) showed a clear separation of metabolomics profiles of BD patients from HC. Statistical analysis of the data revealed differential metabolites between BD patients and HC. The serum levels of some phosphatidylcholines (PCs) were found to be significantly lower in BD patients, while the levels of several polyunsaturated fatty acids (PUFAs) were increased markedly in the BD group compared with HC. Furthermore, the serum level of two omega-6 PUFAs, linoleic acid (LA) and arachidonic acid (AA), were dramatically decreased in patients with remission. A validation cohort confirmed that the serum LA and AA levels in BD patients were significantly higher than those in HC and patients with RA, SLE, TA, and CD. In addition, receiver operating characteristic (ROC) analysis indicated good sensitivity and specificity. Conclusions The serum metabolomics profiles in BD patients are altered. Serum LA and AA are promising diagnostic biomarkers for BD.

A fabricated mesh cage and/or posterior occipitocervical instrumentation alone has been used for reconstruction of ventral defect of the upper cervical spine. However, using a trimmed mesh cage it was hard to achieve optimal clival screw purchase and it migrated or broke. A specific instrumentation at the craniovertebral junction (CVJ) should incorporate the morphology of the CVJ and biomechanical validation. The purpose of the present study was to develop an innovative clivus plate integrated with the clinical anatomy of CVJ and to evaluate the stability of the clivus plate fixation (CPF), stand-alone or combined with a posterior occipitocervical fixation (POCF). Dimensions relevant to the clivus plate were measured on 40 adult dry bones and CT images of 30 patients. The CPF was composed of the clivus plate and a titanium mesh cage. The clivus plate was anchored to the clivus, atlas and C3 body and connected to the mesh cage. Six fresh cadaveric head–neck specimens (Oc–C4) were used in this study (46 ± 15 years old, 2 F/4 M). A continuous pure moment of ±1.5 Nm was applied to the specimen in flexion, extension, lateral bending and axial rotation. The status of intact, CPF alone, and CPF plus POCF was tested on each specimen. The CPF was implanted to the specimen following resection of the C1 anterior arch, C2 vertebral body, C2–C3 disc and atlantoaxial ligaments. The POCF was applied with screws anchoring at the occiput, C1, C3 and C4. The range of motion (ROM) and neutral zone (NZ) from the occiput to C3 were calculated. The clivus plate was developed based on measurements of 40 adult dry bones and CT images of 30 patients. The plates were successfully applied to all specimens. No obvious loosening or mismatch was observed. The mean clival length and widest and narrowest diameter of the clivus were 26, 33 and 19 mm, respectively. The clivus screw length was 8 mm for the caudal holes and 10 mm for the cephalad hole. The CPF reduced ROMs to 3.9° in flexion, 2.8° in extension, 4.2° in lateral bending and 6.8° in axial rotation. The combined CPF and POCF constrained motion within 0.6° in all directions and more than the CPF (P

Due to the mutations of the Bcr/Abl oncogene that obstacle the binding of the protein with imatinib, the resistance to imatinib has developed in a significant portion of chronic myeloid leukemia (CML) patients. It stimulated the search for novel molecules for treatment of imatinib-resistance CML. Inhibiting the amplification of Bcr/Abl oncogene is believed to be a new effective strategy to override the imatinib resistance on CML cells. In present research, we demonstrated that dihydroartemisinin (DHA), a safe and effective antimalarial analog of artemisinin, could significantly inhibit the Bcr/Abl fusion gene at the mRNA level in CML cells sensitive or resistant to imatinib (including the primary CML cells with T315I mutation) and induce cell death. Moreover, dihydroartemisinin could also lead to the inhibition of the Bcr/Abl protein expression and tyrosine kinase activity, and strongly suppress on the downstream signals of Bcr/Abl, which included inhibition of tyrosine kinase activity of AKT and ERK, promotion of cytochrome c release from the mitochondria and the consequential activation of caspase-9/3 in imatinib-resistant CML cells. These results suggest for the first time that Dihydroartemisinin might be a potential novel drug candidate for treatment of imatinib-resistant CML and worthy of further study.

In our previous publication, we have shown that dihydroartemisinin could significantly inhibit the growth of CML K562 cells by its anti-proliferative and inducing apoptotic effects. Given the pivotal effect of Bcr/Abl tyrosine kinase and its downstream signal factors on CML cell proliferation and survival, we extend our study to investigate the effect of DHA on Bcr/Abl and related signal factors to further illuminate the possible mechanisms of the effect of DHA on CML cells.The expression of Bcr/Abl was analyzed with PCR and Western blotting methods at both mRNA and protein levels. Measurement of protein expression and tyrosine phosphorylation activity of Bcr/Abl, AKT, ERK1/2, NF-κB and cytochrome c were performed with Western blotting and immunoprecipitation methods. Using the activity kits analyzed the activity of caspase 9 and caspase 3.The treatment with DHA results in a significant suppression on Bcr/Abl expression and leads to a concentration-dependent reduction on the Bcr/Abl tyrosine activity. Moreover, it also results in a strong influence on the downstream signal factors of Bcr/Abl, which includes inhibition of tyrosine kinase activity of AKT and ERK1/2, suppression of NF-κB protein expression, promotion of the cytochrome c release and the consequential activation of caspase 3/9 in CML K562 cells.Together with our previous report, our data show that the growth inhibitory effect of DHA on CML cells might be due to the influence on Bcr/Abl expression and its downstream signal factors. DHA might be a potential novel anti-CML drug candidate and worthy of further study.

Dentin dysplasia type I (DDI) is an autosomal-dominant genetic disorder resulting from dentin defects. The molecular basis of DDI remains unclear. DDI exhibits unique characteristics with phenotypes featuring obliteration of pulp chambers and diminutive root, thus providing a useful model for understanding the genetics of tooth formation. Using a large Chinese family with 14 DDI patients, we mapped the gene locus responsible for DDI to 3p26.1-3p24.3 and further identified a missense mutation, c.353CA (p.P118Q) in the SSUH2 gene on 3p26.1, which co-segregated with DDI. We showed that SSUH2 (p.P118Q) perturbed the structure and significantly reduced levels of mutant (MT) protein and mRNA compared with wild-type SSUH2. Furthermore, MT P141Q knock-in mice (+/- and -/-) had a unique partial obliteration of the pulp cavity and upregulation or downregulation of six major genes involved in odontogenesis: Dspp, Dmp1, Runx2, Pax9, Bmp2, and Dlx2. The phenotype of missing teeth was determined in zebrafish with morpholino gene knockdowns and rescued by injection of normal human mRNA. Taken together, our observations demonstrate that SSUH2 disrupts dental formation and that this novel gene, together with other odontogenesis genes, is involved in tooth development.