Topiramate use in a pediatric patient with comorbid bipolar disorder and trichotillomania: A 3-year follow-up.

Trichotillomania (TTM) is an intractable and chronic mental disorder that causes significant distress or functional impairments in various life domains. Most individuals with trichotillomania have other comorbid diagnoses. Bipolar disorder (BD) is one of the most common comorbid conditions. Up to date, no FDA-approved drugs for TTM are available, not to mention children and adolescent patients with TTM and BD. Here, we present a case of an 8-year-old child with a long history of episodic TTM and bipolar disorder who was effectively treated with topiramate in a 3-year follow-up.

The impact of comorbid premenstrual syndrome or premenstrual dysphoric disorder on the clinical characteristics of bipolar disorder among Han Chinese women.

Bipolar disorder (BD) is commonly comorbid with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD). However, little is known about their relationship. This study aimed to assess the impact of comorbid PMS or PMDD on the clinical characteristics of BD. A cross-sectional study was conducted on 262 women with BD. PMS and PMDD were screened with the Premenstrual Symptoms Screening Tool (PSST). Symptomatic features were assessed with Hamilton Depression Scale (HAMD), Young Mania Rating Scale (YMRS), and atypical features by the depressive episode section of SCID-I/P. The rates of PMS and PMDD among BD were 57.6% and 20.6% according to PSST. No significant difference in the rates of PMS and PMDD was found between BD I, BD II, and BD-NOS. Compared to BD patients without PMS or PMDD, patients with comorbid BD and PMS or PMDD were younger, more educated, had a higher risk of OCD, had an earlier age of onset, scored higher on HAMD-17 and its sub-scale of anxiety/somatization, cognitive deficit, psychomotor retardation, and were more likely to have increased appetite and leaden paralysis. In addition, patients with comorbid BD and PMDD were less likely to experience traumatic life events, more likely to have family history of mental disorders and have inflammatory or autoimmune disease, scored higher on HMAD-17, particularly in its sub-scale of anxiety/somatization, cognitive deficit, psychomotor retardation, and sleep disturbance. Compared with BD without PMS or PMDD, BD with PMS or PMDD might be a specific subtype of BD characterized with earlier onset age, heavier genetic load, increased symptom severity, and atypical features.

METTL3-mediated m6A RNA methylation induces the differentiation of lung resident mesenchymal stem cells into myofibroblasts via the miR-21/PTEN pathway.

BACKGROUND: The accumulation of myofibroblasts is the key pathological feature of pulmonary fibrosis (PF). Aberrant differentiation of lung-resident mesenchymal stem cells (LR-MSCs) has been identified as a critical source of myofibroblasts, but the molecular mechanisms underlying this process remain largely unknown. In recent years, N6-methyladenosine (m6A) RNA modification has been implicated in fibrosis development across diverse organs; however, its specific role in promoting the differentiation of LR-MSCs into myofibroblasts in PF is not well defined. METHODS: In this study, we examined the levels of m6A RNA methylation and the expression of its regulatory enzymes in both TGF-ß1-treated LR-MSCs and fibrotic mouse lung tissues. The downstream target genes of m6A and their related pathways were identified according to a literature review, bioinformatic analysis and experimental verification. We also assessed the expression levels of myofibroblast markers in treated LR-MSCs and confirmed the involvement of the above-described pathway in the aberrant differentiation direction of LR-MSCs under TGF-ß1 stimulation by overexpressing or knocking down key genes within the pathway. RESULTS: Our results revealed that METTL3-mediated m6A RNA methylation was significantly upregulated in both TGF-ß1-treated LR-MSCs and fibrotic mouse lung tissues. This process directly led to the aberrant differentiation of LR-MSCs into myofibroblasts by targeting the miR-21/PTEN pathway. Moreover, inhibition of METTL3 or miR-21 and overexpression of PTEN could rescue this abnormal differentiation. CONCLUSION: Our study demonstrated that m6A RNA methylation induced aberrant LR-MSC differentiation into myofibroblasts via the METTL3/miR-21/PTEN signaling pathway. We indicated a novel mechanism to promote PF progression. Targeting METTL3-mediated m6A RNA methylation and its downstream targets may present innovative therapeutic approaches for the prevention and treatment of PF.

Identifying Candidate Genes Associated with Sporadic Amyotrophic Lateral Sclerosis via Integrative Analysis of Transcriptome-Wide Association Study and Messenger RNA Expression Profile.

Amyotrophic lateral sclerosis, a fatal neurodegeneration disease affecting motor neurons in the brain and spinal cord, is difficult to diagnose and treat. The objective of this study is to identify novel candidate genes related to ALS. Transcriptome-wide association study of ALS was conducted by integrating the genome-wide association study summary data (including 1234 ALS patients and 2850 controls) and pre-computed gene expression weights of different tissues. The ALS-associated genes identified by TWAS were further compared with the differentially expressed genes detected by the mRNA expression profiles of the sporadic ALS. Functional enrichment and annotation analysis of identified genes were performed by an R package and the functional mapping and annotation software. TWAS identified 761 significant genes (PTWAS < 0.05), 627 Gene ontology terms, and 8 Kyoto Encyclopedia of Genes and Genomes pathways for ALS, such as C9orf72, with three expression quantitative trait loci were found significantly: rs2453554 (PTWAS CBRS = 4.68 × 10-10, PTWAS CBRS = 2.54 × 10-9), rs10967976 (PTWAS CBRS = 7.85 × 10-10, PTWAS CBRS = 8.91 × 10-9, PTWAS CBRS = 1.49 × 10-7, PTWAS CBRS = 5.59 × 10-7), rs3849946 (PTWAS CBRS = 7.69 × 10-4, PTWAS YBL = 4.02 × 10-2), Mitochondrion (Padj = 4.22 × 10-16), and Cell cycle (Padj = 2.04 × 10-3). Moreover, 107 common genes, 4 KEGG pathways and 41 GO terms were detected by integrating mRNA expression profiles of sALS, such as CPVL (FC = 2.06, PmRNA = 6.99 × 10-6, PTWAS CBR = 2.88 × 10-2, PTWAS CBR = 4.37 × 10-2), Pyrimidine Metabolism (Padj = 2.43 × 10-2), and Cell Activation (Padj = 5.54 × 10-3). Multiple candidate genes and pathways were detected for ALS. Our findings may provide novel clues for understanding the genetic mechanism of ALS.

SMPDL3B contributes to gastric adenocarcinoma cells progression by promoting the infiltration of M2 macrophages.

Background/aim: The common disease gastric adenocarcinoma (GAC) has a high morbidity and mortality, so there is an urgent need for research to explore new diagnostic markers and therapeutic targets. This investigation was carried out to investigate the expression of sphingomyelin phosphodiesterase acid-like 3b (SMPDL3B) in GAC and its effects on tumor progression. Materials and methods: Samples were collected from patients who underwent radical gastrectomy from January 2021 to December 2022. Along with the normal gastric epithelial cell lines GES-1 and SGC-7901, the AGS, MGC-803, and MSN-45 human gastric cancer cell lines were used to confirm SMPDL3B expression. RT-qPCR, Western blot, immunohistochemical, cell proliferation, assay of wound healing, transwell migration assay, invasion assay, flow cytometry, and immune evaluation experiments were carried out. Results: SMPDL3B was found to be substantially expressed in GAC, and this condition has a bad prognosis. By establishing SMPDL3B knockdown and overexpression of GAC cell lines, this study confirmed that SMPDL3B promoted tumor cell proliferation, migration, and invasion. Additional bioinformatics research revealed a connection between SMPDL3B and immune cell infiltration in the GAC immunological microenvironment, which enhanced tumor cell proliferation by promoting the infiltration content of M2 macrophages. Conclusion: This study determined the function of SMPDL3B for the clinical diagnosis, prediction, and novel management of GAC.

Neuropsychiatric lupus erythematosus with neurogenic pulmonary edema and anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor limbic encephalitis: a case report.

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.

Ketone Metabolite ß-Hydroxybutyrate Ameliorates Inflammation After Spinal Cord Injury by Inhibiting the NLRP3 Inflammasome.

Ketogenic diet (KD) has been shown to be beneficial in a range of neurological disorders, with ketone metabolite ß-hydroxybutyrate (ßOHB) reported to block the nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in bone marrow-derived macrophages. In this study, we show that pretreatment with KD or in situ ßOHB suppressed macrophages/microglia activation and the overproduction of inflammatory cytokines, while KD downregulated the expression of NLRP3 inflammasome. Moreover, KD promoted macrophages/microglia transformation from the M1 phenotype to the M2a phenotype following spinal cord injury (SCI) in the in vivo study. Rats in the KD group demonstrated improved behavioral and electrophysiological recovery after SCI when compared to those rats in the standard diet group. The in vitro study performed on BV2 cells indicated that ßOHB inhibited an LPS+ATP-induced inflammatory response and decreased NLRP3 protein levels. Our data demonstrated that pretreatment with KD attenuated neuroinflammation following SCI, probably by inhibiting NLRP3 inflammasome and shifting the activation state of macrophages/microglia from the M1 to the M2a phenotype. Therefore, the ketone metabolite ßOHB might provide a potential future therapeutic strategy for SCI.

Aberrant FcγRIIb and FcγRIII expression on monocytes from patients with Behçet's disease.

Behçet'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.

[Management of a colon cancer patient complicated with COVID-19].

OBJECTIVE: To explore the feasibility of radical resection for cancer patients complicated with coronavirus disease 2019 (COVID-19). METHODS: The management and clinical outcome of a sigmoid cancer patient with COVID-19 were analyzed. RESULTS: The inflammation indicators and fever of this patient were effectively controlled and the lung lesions remained stable after active anti-viral treatment, then the radical colorectomy was performed after the viral negative conversion for twice. CONCLUSIONS: The case indicates that radical resection can be performed in SARS-CoV-2 patients with twice-negative SARS-CoV-2 nucleic acid testing results.

Metformin Alleviates the Bone Loss Induced by Ketogenic Diet: An In Vivo Study in Mice.

Metformin (Met), an anti-diabetes drug, has also shown therapeutic effects for ovariectomy-induced (OVX) osteoporosis. However, similar effects against bone loss induced by a ketogenic diet (KD) have not been tested. This study was aimed to evaluate the microarchitectures and biomechanics of KD-induced osteoporosis with and without administration of Met, and compare the effect of Met on bone loss induced by KD with OVX. Forty female C57BL/6J mice were randomly divided into Sham, OVX, OVX + Met (100 mg/kg/day), KD (3:1 ratio of fat to carbohydrate and protein), and KD + Met (100 mg/kg/day) groups. After 12 weeks, the bone mass and biomechanics were measured in distal cancellous bone and in mid-shaft cortical bone of the femur. The activities of serum alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP), together with immunohistochemistry staining of osteocalcin (OCN) and TRAP, were evaluated. Both OVX and KD induced significant bone loss and compromised biomechanical properties in the cancellous bone, but no effect was found in cortical bone. The administration of Met increased the cancellous bone volume fraction (BV/TV) from 3.78 to 5.23% following the OVX and from 4.04 to 6.33% following the KD, it also enhanced the compressive stiffness from 47 to 160 N/mm following the OVX and from 35 to 340 N/mm with the KD. Met effectively increased serum ALP in the KD group while decreased serum TRAP in the OVX group, but up-regulated expression of OCN and down-regulated expression of TRAP in both OVX and KD groups. The present study demonstrated that Met effectively attenuated the cancellous bone loss induced by KD and maintained the biomechanical properties of long bones, providing evidence for Met as a treatment of by KD-induced osteoporosis in teenage skeleton.

Ketogenic diet compromises vertebral microstructure and biomechanical characteristics in mice.

Ketogenic diet (KD) compromised the microstructure of cancellous bone and the mechanical property in the appendicular bone of mice, while the effects of KD on the axial bone have not been reported. This study aimed to compare the changes in the microstructure and mechanical properties of the forth lumbar (L4) vertebra in KD and ovariectomized (OVX) mice. Forty eight-week-old female C57BL/6J mice were assigned into four groups: SD (standard diet) + Sham, SD + OVX, KD + Sham, and KD + OVX groups. L4 vertebra was scanned by micro-CT to examine the microstructure of cancellous bone, after which simulative compression tests were performed using finite element (FE) analysis. Vertebral compressive test and histological staining of the L4 and L5 vertebrae were performed to observe the biomechanical and histomorphologic changes. The KD + Sham and SD + OVX exhibited a remarkable declination in the parameters of cancellous bone compared with the SD + Sham group, while KD + OVX demonstrated the most serious bone loss in the four groups. The stiffness was significantly higher in the SD + Sham group than the other three groups, but no difference was found between the remaining groups. The trabecular parameters were significantly correlated with the stiffness. Meanwhile, the OVX + Sham and KD + OVX groups showed a significant decrease in the failure load of compressive test, while there was no difference between the KD + Sham and SD + Sham groups. These findings suggest that KD may compromise the vertebral microstructure and compressive stiffness to a similar level as OVX did, indicating adverse effects of KD on the axial bone of the mice.

Combination of Colour Duplex and Contrast Enhanced Ultrasound as an Alternative to Computed Tomography Angiography in Isolated Mesenteric Artery Dissection Surveillance.

OBJECTIVES: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: The combination of CDU and CEUS can be used in place of CTA for the surveillance of IMAD.

Diagnostic value of the interferon-γ release assay for tuberculosis infection in patients with Behçet's disease.

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.

Rapid cycling bipolar disorder is associated with antithyroid antibodies, instead of thyroid dysfunction.

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.

Ketogenic diet delays spinal fusion and decreases bone mass in posterolateral lumbar spinal fusion: an in vivo rat model.

BACKGROUND: Ketogenic diet (KD), a low-carbohydrate-and-high-fat diet, causes a metabolic state of ketogenesis and has been used to treat drug-resistance epilepsy. Our recent studies showed KD neuroprotective after spinal cord injury and causing bone loss. Effects of KD on spinal fusion were still unknown. This study was aimed to evaluate effects of KD on spinal fusion in rats. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into KD and standard diet (SD) groups. The KD group was fed with food of 1:4 carbohydrates to fat. All rats were subjected to L4/5 posterolateral lumbar spinal fusion. The blood ketone, and serum calcium, phosphorus, and insulin-like growth factor-1 (IGF-1) were measured, as well as the fusion rates, bone mass (BV), and bone mineral contents (BMC) of fusion sites were estimated at 4 and 8 weeks. RESULTS: There was no significant difference in serum calcium or phosphorus levels between groups at 4 or 8 weeks. However, there was a significant increase of blood ketone (1.02 mmol/L vs 0.38 mmol/L at 4 weeks; 0.83 mmol/L vs 0.32 mmol/L, at 8 weeks) and decrease of serum IGF-1 (339.4 ng/mL vs 630.6 ng/mL at 4 weeks; 418.8 ng/mL vs 628.6 ng/mL, at 8 weeks) in the KD group compared with the SD group. The spinal fusion occurred less in the KD group (1/16 vs 6/16 at 4 weeks; 7/16 vs 10/16, at 8 weeks), particularly at 4 weeks after surgery. The BV and BMC were lower in the KD group than that in the SD group at 4 weeks, but not different between groups at 8 weeks. CONCLUSIONS: This study demonstrated that KD delayed spinal fusion and decreased bone mass in posterolateral lumbar spinal fusion in rats.

Mutation in SSUH2 Causes Autosomal-Dominant Dentin Dysplasia Type I.

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.353C>A (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.

Ketogenic Diet Compromises Both Cancellous and Cortical Bone Mass in Mice.

To clarify osteoporotic effects of ketogenic diet (KD) on cancellous and cortical bone compared with ovariectomy (OVX) in mice. Forty female C57BL/6J 8-week-old mice were randomly divided into SD+Sham, SD+OVX, KD+Sham, and KD+OVX groups, and fed for 12 weeks. The distal femur of trabecular bone and the middle femur of cortical bone were evaluated with Micro-CT scanning. The maximum bending force and stiffness of the tibia were calculated using a three-point bending test. Osteoblast and osteoclast expression of femur were identified using tartrate-resistant acid phosphatase (TRAP), collagen type I (CoLI), and osteocalcin (OCN) staining. A 2-factor analysis of variance was used to evaluate effects of KD and OVX on radiological, biomechanical, and histological parameters. KD resulted in not only remarkable cancellous bone decline comparable to OVX, but also unique cortical bone reduction. The maximum bending force and stiffness decreased in the KD+Sham and KD+OVX groups but did not change in the SD+OVX group. The KD+OVX led to significantly higher expression in TRAP and noticeably lower expression in CoLI when compared with other groups. Both KD+Sham and SD+OVX prominently increased expression in TRAP, but decreased expression in CoLI. There was no significant difference in OCN among the four groups. The present results suggest that KD compromises both the cancellous and cortical bone architecture of long bones while OVX only in cancellous bone architecture. A combination of KD and OVX may lead to more bone loss.

Symptomatic knee osteonecrosis in patients with systemic lupus erythematosus: a case-control study.

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.

A clivus plate fixation for reconstruction of ventral defect of the craniovertebral junction: a novel fixation device for craniovertebral instability.

PURPOSE: 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). METHODS: 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. RESULTS: 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 < 0.05). NZs after the CPF were 1.0° in flexion-extension, 2.1° in lateral bending and 2.2° in axial rotation, respectively. NZs after the CPF plus POCF were within 0.2° in all directions and less than the CPF (P < 0.05). CONCLUSION: This study demonstrated screw purchase in the adult clivus and developed an innovative clivus plate fixation for reconstructing an extensive ventral defect in the upper cervical spine. The clivus plate fixation combined a posterior instrumentation ensuring reliable upper cervical stability.

The effects of osteoporosis and disc degeneration on vertebral cartilage endplate lesions in rats.

PURPOSE: Evidence has shown that osteoporosis or intervertebral disc degeneration (IDD) led to cartilage endplate lesions (CEL), but their combined effects on the lesion remain unknown. This study developed an innovative rat model combined ovariectomy (OVX) and cervical muscle section (CMS), and aimed to evaluate the combined effects of osteoporosis and IDD on cartilage endplate lesions of cervical spine. METHODS: Fifty-two Sprague-Dawley female rats were assigned randomly into four groups as follows: the sham group (n = 10) underwent sham surgery; the OVX group (n = 14) was subjected to bilateral ovariectomy; the CMS group (n = 14) had posterior paraspinal muscles cut from C2 to C7; the CMS-OVX group (n = 14) underwent the OVX and CMS surgeries consecutively. Samples of C6-C7 segments were harvested at 12, 18 and 24 weeks post-surgery. Micro-CT analysis was performed to evaluate the CEL, intervertebral disc height (IDH) and structural indices. Histological analysis with Safranine O/fast green stain and histological score were used to observe the characteristics of the degenerative discs. RESULTS: Ovariectomy surgery resulted in significant changes of most structural indices of the C6 body, such as decrease of percent bone volume and number of bone trabecula at 12 weeks, and greater changes at 18 and 24 weeks. The CEL following CMS surgery was seen on the ventral, while the CEL in the OVX and sham groups on the peripheral. The CEL was greatest in the CMS-OVX group and significantly greater than that in the CMS and OVX groups at 12 and 18 weeks (P < 0.05). The CMS surgery resulted in significant IDH decrease at 12, 18 and 24 weeks (P < 0.05), while the OVX surgery resulted in mild IDH decrease when compared with the sham group. The IDH in the CMS-OVX group was significantly lower than that in the CMS group at 24 weeks (P < 0.05). Histological evaluation suggested cartilage endplate abrasion at 12 weeks, and in situ calcification at 18 and 24 weeks in the CMS and CMS-OVX groups. Disc degenerative scores were higher following CMS or OVX surgery, and correlated with the CEL and IDH (P < 0.01), respectively. CONCLUSIONS: The present study suggested that a combination of OVX and CMS led to more lesion of cartilage endplate than any one thereof, as well as more decrease of IDH. The lesion and IDH decrease were associated with the disc degeneration levels. The cartilage endplate was worn out at the early stage and calcified in situ later. The results indicate that osteoporosis may deteriorate the disc degeneration at specific time.