L4/5 Disc Herniation: Not Unusually Accompanied with L5/S1 Low-Grade Spondylolytic Spondylolisthesis.

OBJECTIVE: Isthmic spondylolisthesis (IS) is distinguished by a congenital defect or acquired fracture of the pars interarticularis. Numerous studies on L5 low-grade IS have been carried out; however, there is a paucity of data regarding the condition of L5 IS concomitant with L4/5 disc herniation. This study aimed to identify the incidence rate and to illustrate the possible risk factors for L4/5 disc herniation in L5 low-grade IS patients. METHODS: A total of 268 consecutive patients diagnosed as L5/S1 low-grade IS between May 2017 and May 2022 were retrospectively enrolled in this study. Depending on the presence of L4/5 disc herniation or not, patients were divided into an L4/5 disc herniation group (L4/5 DH) and an L4/5 non-disc herniation group (L4/5 non-DH). Radiographic parameters were measured, and the ratios of L4-S1 segmental lordosis (SL) to lumbar lordosis (LDI), L4 inferior endplate (IEP) to L5 superior endplate (SEP) (L4 IEP/L5 SEP), and L5 IEP to S1 SEP (L5 IEP/S1 SEP) were compared between groups. The Pfirrmann grade of the L4/5 disc and the L5/S1 disc, and Roussouly classifications of each patient were also recorded. Univariate analysis (including independent-samples t-test and χ2 -test) and multiple logistic regression analysis were performed to analyze the data. RESULTS: There were 40 patients (14.9%) in the L4/5 DH group. The Roussouly classification differed significantly between groups. As demonstrated by the Pfirrmann grade, the L4/5 DH group showed more advanced disc degeneration at L4/5 than the L4/5 non-DH group. In contrast to the L4/5 non-DH group, the L4/5 DH group had a significantly larger L4 IEP, L4 IEP/L5 SEP, S1 SEP, and LDI while smaller L4/5 disc angle, L4/5 disc height, slip percentage, lumbar lordosis, and sacral slope. Multivariate logistic regression analysis revealed that higher L4/5 disc Pfirrmann grade (p = 0.004), decreased L4/5 disc height (p < 0.001), and lower L5 slip percentage (p = 0.022) were significantly associated with the occurrence of L4/5 DH. CONCLUSIONS: L4/5 disc herniation is not unusually accompanied by L5/S1 low-grade IS. Advanced L4/5 disc degeneration, decreased L4/5 disc height, and lower L5 slip percentage might be significantly associated with L4/5 disc herniation.

Not All Osteophytes Are Located on the Right Side of the Vertebrae in Diffuse Idiopathic Skeletal Hyperostosis: A Quantitative Analysis in Relation to the Position of Aorta.

OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by osteophytes in the anterior vertebrae, and the presence of aorta may have an impact on their formation. However, the anatomical positional relationship between the aorta and osteophytes in patients with DISH remains controversial. This study aimed to evaluate the position of osteophytes in relation to aorta in DISH, and the influence of aortic pulsation on the formation of osteophytes from the perspective of morphology. METHODS: We conducted a retrospective review of 101 patients diagnosed with DISH and symptomatic lumbar spinal stenosis between June 2018 and December 2021. A total of 637 segments with heterotopic ossification in DISH were used for quantitative measurements on CT scans. The Cartesian coordinate system was built up on the axial CT scans to reflect the relative position between aorta and osteophytes. Osteophytes were divided into adjacent aorta group (AD group) and non-adjacent aorta group (N-AD group). In terms of the morphology, osteophytes in the AD group were further divided into convex, flat, and concave types. The relative position between aorta and osteophytes, and the aorta-osteophyte distance and morphology of osteophytes were compared. Univariate analysis of variance was performed for multiple groups, and two independent-samples t-tests were used for two groups. RESULTS: From T5 to L4, aorta gradually descended from left side to middle of vertebrae, and osteophytes gradually shifted from right side of vertebrae (T5-T10) to bilateral sides (T11-L4). Of 637 osteophytes in DISH, 60.1% (383/637) were in AD group, including convex type 0.6% (4/637), flat type 34.7% (221/637), and concave type 24.8% (158/637). The N-AD group accounted for 39.9% (254/637). Flat osteophytes were concentrated in T5-T12, while concave osteophytes in T11-L4. Overall, the aorta-osteophyte distance of concave type was significantly smaller than that of flat type. CONCLUSION: Osteophytes are not always located on the right side of vertebrae, but move with the position of the descending aorta. Furthermore, the morphology of osteophytes varies by vertebral segment in DISH, which is related to aorta descending anteriorly in the spine.

How does diffuse idiopathic skeletal hyperostosis affect the sagittal spinopelvic alignment in lumbar spinal stenosis patients?

OBJECTIVE: To compare the differences of spinopelvic morphology among patients with DISH, patients without DISH and normal elderly and to assess the impact of ossification extent on sagittal alignment. METHODS: Patients with and without DISH aged > 50 years who required surgery because of lumbar spinal stenosis were enrolled in this cohort(DISH and Non-DISH groups). Also, we collected age-matched normal old outpatients as the control group(Normal group). According to ossification extent, DISH group were divided into two subgroups(T-DISH and L-DISH subgroups). Spinopelvic parameters were measured. Distribution differences of Roussouly classification were analyzed between DISH and Non-DISH group, T-DISH and L-DISH subgroup, respectively. Additionally, distribution difference of kyphotic apex vertebrae between T-DISH and L-DISH subgroup was also investigated. RESULTS: A total of 429 patients (300 males and 129 females) were enrolled in our study, with a mean age of 64.1 ± 5.8 years. Compared to the Normal group, DISH and Non-DISH groups both had significantly higher CSVA, PT, OH, SVA, TPA and lower LL, SS, C7 Tilt, SSA, SPA. Compared to Non-DISH group, DISH group, regardless of ossification extent, had significantly higher T1 slope, CSVA, TK and SVA. Besides, T-DISH subgroup showed significant higher LL, PI, SS and SSA than L-DISH subgroup. There were significant differences of Roussouly classification distribution between T-DISH and L-DISH subgroup. In terms of kyphotic apex location, compared to relatively higher locations in T-DISH subgroup, L-DISH subgroup had apical locations predominantly in the lower thoracic. CONCLUSION: Sagittal spinopelvic alignment is influenced by the presence of DISH and the extent of ossification. Patients with L-DISH have not only increased thoracic kyphosis and forward trunk, but also insufficient lumbar lordosis.

Circular RNA circ_0062389 modulates papillary thyroid carcinoma progression via the miR-1179/high mobility group box 1 axis.

Circular RNAs (circRNAs) feature prominently in regulating the progression of tumors, including papillary thyroid carcinoma (PTC). This work is designated to delve into the role of circ_0062389 in PTC. Generally, quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect circ_0062389, miR-1179 and high mobility group box 1 (HMGB1) mRNA expression levels. RNase R assay was used to verify the circular characteristics of circ_0062389. After circ_0062389 was knocked down in PTC cells, CCK-8 assay was adopted to determine cell viability. Wound healing assay was leveraged to probe cell migration. Besides, Western blot assay was executed to examine the expression levels of HMGB1 and epithelial-mesenchymal transformation (EMT)-related markers (E-cadherin and N-cadherin). Dual-luciferase reporter assay was performed to authenticate the targeting relationships between miR-1179 and circ_0062389, as well as miR-1179 and HMGB1. Here, this work proved that circ_0062389 was greatly up-regulated in PTC tissues and cell lines. The high expression of circ_0062389 was related to large tumor size and positive lymphatic metastasis. Knocking down circ_0062389 could inhibit the proliferation, migration and EMT process of PTC cells. Besides, miR-1179 was a downstream molecule of circ_0062389. Furthermore, miR-1179 inhibitors could partially reverse the above effect of knocking down circ_0062389 on PTC cells. It was also confirmed that HMGB1 was a direct target of miR-1179 and mediated the effects of circ_0062389 and miR-1179 in PTC. Altogether, circ_0062389 can adsorb miR-1179, and regulate HMGB1 expression, thus playing a role in PTC.

Long non-coding RNA PITPNA-AS1 regulates UNC5B expression in papillary thyroid cancer via sponging miR-129-5p.

BACKGROUND: Long non-coding RNA (lncRNA) PITPNA antisense RNA 1 (PITPNA-AS1) expression characteristics, function, and mechanism in papillary thyroid cancer are unclear. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for detecting PITPNA-AS1, UNC-5 netrin receptor B (UNC5B) mRNA, and miR-129-5p expressions in papillary thyroid cancer tissues and cell lines. EdU assay, cell counting kit-8 (CCK-8) assay, wound healing assay, and flow cytometry analysis were performed to investigate the biological functions of PITPNA-AS1 in papillary thyroid cancer. Dual-luciferase reporter assay was utilized for determining whether PITPNA-AS1 and miR-129-5p, as well as UNC5B and miR-129-5p could directly bind to each other. Western blot assay was employed for measuring UNC5B protein expression level in papillary thyroid cancer cell lines. RESULTS: PITPNA-AS1 and UNC5B expressions were markedly increased in papillary thyroid cancer tissues and cell lines while miR-129-5p expression was down-regulated. Knockdown of PITPNA-AS1 could significantly inhibit papillary thyroid cancer cell growth and migration and promote cell apoptosis while UNC5B overexpression plasmids or miR-129-5p inhibitors counteracted the knockdown effect of PITPNA-AS1 on papillary thyroid cancer cells. PITPNA-AS1 targeted miR-129-5p to repress its expression and miR-129-5p targeted UNC5B to repress its expression. Silencing PITPNA-AS1 reduced the expression of UNC5B via regulating miR-129-5p expression. CONCLUSIONS: PITPNA-AS1 facilitated papillary thyroid cancer cell proliferation and migration, and suppressed apoptosis through miR-129-5p/UNC5B axis.

Low serum choline and high serum betaine levels are associated with favorable components of metabolic syndrome in Newfoundland population.

BACKGROUND: We investigated the relationships between serum choline and betaine levels with metabolic syndrome-related indices in the general population of Newfoundland. METHODS: 1081 adults were selected from the CODING study. Serum choline and betaine levels were measured. Major confounding factors were controlled in all analyses. RESULTS: Partial correlation and linear regression analysis showed that serum choline levels were positively associated with systolic blood pressure (r: 0.124), serum TG levels (r: 0.132) and negatively correlated with serum glucose levels (r: -0.121) in males (p < 0.01 for all). In females, serum choline levels were positively correlated with serum TG, TC and HDL levels (r: 0.104 to 0.148, p < 0.05 for all). Serum betaine levels were negatively associated with serum TG, TC, LDL and insulin levels, and with atherogenic index and HOMA-IR index in males (r: -0.081 to -0.179, p < 0.05 for all). In females, serum betaine levels were negatively associated with serum TG, hsCRP and insulin levels, and with HOMA-IR index (r: -0.092 to -0.213, p < 0.05 for all). Moreover, subjects with serum choline levels in the highest tertile showed highest serum TG levels and systolic blood pressure in males, and highest serum lipids levels in females. Subjects with the highest serum betaine levels had the lowest serum lipids levels, atherogenic index, IR severity in males, and the lowest serum TG and hsCRP levels, and IR severity in females. CONCLUSION: Low serum choline and high serum betaine levels are associated with favorable components of metabolic syndrome in general adults.

Higher serum choline and betaine levels are associated with better body composition in male but not female population.

BACKGROUND: Animal studies proved that choline and betaine have beneficial effect on reducing body fat. However, evidence in humans is scarce. We aim to investigate the association between serum choline and betaine levels with body composition in general population. METHODS: This is an observational cross-sectional study performed in 1081 subjects from the CODING (Complex Disease in Newfoundland population: Environment and Genetics) study. Serum choline and betaine levels were measured based on liquid chromatography coupled with tandem mass spectrometry technology. Body composition was measured using dual-energy X-ray absorptiometry following a 12-hour fast. Major confounding factors including age, sex, total calorie intake and physical activity level were controlled in all analyses. RESULTS: Significantly inverse correlations were found between serum betaine levels and all obesity measurements in males (r ranged from -0.12 to -0.23, and p<0.01 for all) but not in females. Serum choline was negatively associated with total percent body fat (%BF), percent trunk fat (%TF), weight, body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (r ranged from -0.11 to -0.19, and p<0.05 for all) in males and positively associated with weight, BMI and WC (r ranged from 0.09 to 0.10, and p<0.05 for all) in females. The negative associations between serum choline and betaine levels with obesity in males were more profound in those not on any medication than those taking medications. Moreover, obese males had the lowest serum choline and betaine levels, followed by overweight males, and normal weight males having the highest serum choline and betaine levels, especially in those not taking medications (p<0.05). Likewise, subjects with the highest serum levels of both had the lowest obesity indexes, especially those not taking medications. CONCLUSIONS: Higher serum choline and betaine levels were associated with a more favorable body composition (lower body fat and higher lean body mass) in males and the favorable association was more pronounced in non-medication users.

Epigallocatechin gallate (EGCG) suppresses lipopolysaccharide-induced Toll-like receptor 4 (TLR4) activity via 67 kDa laminin receptor (67LR) in 3T3-L1 adipocytes.

Obesity-related insulin resistance is associated with chronic systemic low-grade inflammation, and toll-like receptor 4 (TLR4) regulates inflammation. We investigated the pathways involved in epigallocatechin gallate (EGCG) modulation of insulin and TLR4 signaling in adipocytes. Inflammation was induced in adipocytes by lipopolysaccharide (LPS). An antibody against the 67 kDa laminin receptor (67LR, to which EGCG exclusively binds) was used to examine the effect of EGCG on TLR4 signaling, and a TLR4/MD-2 antibody was used to inhibit TLR4 activity and to determine the insulin sensitivity of differentiated 3T3-L1 adipocytes. We found that EGCG dose-dependently inhibited LPS stimulation of adipocyte inflammation by reducing inflammatory mediator and cytokine levels (IKKß, p-NF-κB, TNF-α, and IL-6). Pretreatment with the 67LR antibody prevented EGCG inhibition of inflammatory cytokines, decreased glucose transporter isoform 4 (GLUT4) expression, and inhibited insulin-stimulated glucose uptake. TLR4 inhibition attenuated inflammatory cytokine levels and increased glucose uptake by reversing GLUT4 levels. These data suggest that EGCG suppresses TLR4 signaling in LPS-stimulated adipocytes via 67LR and attenuates insulin-stimulated glucose uptake associated with decreased GLUT4 expression.