Development and evaluation of robot-assisted ultrasound navigation system for pedicle screw placement: An ex-vivo animal validation.

PURPOSE: Spinal instrumentation with pedicle screw placement (PSP) is an important surgical technique for spinal diseases. Accurate screw trajectory is a prerequisite for PSP. Ultrasound (US) imaging with robot-assisted system forms a non-radiative alternative to provide precise screw trajectory. This study reports on the development and assessment of US navigation for this application. METHODS: A robot-assisted US reconstruction was proposed and an automatic CT-to-US registration algorithm was investigated, allowing the registration of screw trajectories. Experiments were conducted on ex-vivo lamb spines to evaluate system performance. RESULTS: In total, 72 screw trajectories are measured, displaying an average position accuracy of 2.80 ± 1.14 mm and orientation accuracy of 1.38 ± 0.61°. CONCLUSION: The experimental results demonstrate the feasibility of proposed US system. This work, although restricted to laboratory settings, encourages further exploration of the potential of this technology in clinical practice.

Metabolic Signature of Healthy Lifestyle and Risk of Rheumatoid Arthritis: Observational and Mendelian Randomization Study.

BACKGROUND: Although substantial evidence reveals that healthy lifestyle behaviors are associated with a lower risk of rheumatoid arthritis (RA), the underlying metabolic mechanisms remain unclear. OBJECTIVES: This study aimed to identify the metabolic signature reflecting a healthy lifestyle and investigate its observational and genetic linkage with RA risk. METHODS: This study included 87,258 UK Biobank participants (557 cases with incident RA) aged 37-73 y with complete lifestyle, genotyping, and nuclear magnetic resonance (NMR) metabolomics data. A healthy lifestyle was assessed based on 5 factors: healthy diet, regular exercise, not smoking, moderate alcohol consumption, and normal body mass index. The metabolic signature was developed by summing the selected metabolites' concentrations weighted by the coefficients using elastic net regression. We used the multivariate Cox model to assess the associations between metabolic signatures and RA risk, and examined the mediating role of the metabolic signature in the impact of a healthy lifestyle on RA. We performed genome-wide association analysis (GWAS) to obtain genetic variants associated with the metabolic signature and then conducted Mendelian randomization (MR) analyses to detect causality. RESULTS: The metabolic signature comprised 81 metabolites, robustly correlated with a healthy lifestyle (r = 0.45, P = 4.2 × 10-15). The metabolic signature was inversely associated with RA risk (HR per standard deviation (SD) increment: 0.76; 95% CI: 0.70-0.83), and largely explained the protective effects of healthy lifestyle on RA with 64% (95% CI: 50.4-83.3) mediation proportion. 1- and 2-sample MR analyses also consistently showed the associations of genetically inferred per SD increment in metabolic signature with a reduction in RA risk (HR: 0.84; 95% CI: 0.75-0.94; and P = 0.002 and OR: 0.84; 95% CI: 0.73-0.97; and P = 0.02, respectively). CONCLUSIONS: Our findings implicate that the metabolic signature reflecting healthy lifestyle is a potential causal mediator in the development of RA, highlighting the importance of early lifestyle intervention and metabolic status tracking for precise prevention of RA.

Robot-assisted ultrasound reconstruction for spine surgery: from bench-top to pre-clinical study.

PURPOSE: Robot-assisted ultrasound (rUS) systems have already been used to provide non-radiative three-dimensional (3D) reconstructions that form the basis for guiding spine surgical procedures. Despite promising studies on this technology, there are few studies that offer insight into the robustness and generality of the approach by verifying performance in various testing scenarios. Therefore, this study aims at providing an assessment of a rUS system, with technical details from experiments starting at the bench-top to the pre-clinical study. METHODS: A semi-automatic control strategy was proposed to ensure continuous and smooth robotic scanning. Next, a U-Net-based segmentation approach was developed to automatically process the anatomic features and derive a high-quality 3D US reconstruction. Experiments were conducted on synthetic phantoms and human cadavers to validate the proposed approach. RESULTS: Average deviations of scanning force were found to be 2.84±0.45 N on synthetic phantoms and to be 5.64±1.10 N on human cadavers. The anatomic features could be reliably reconstructed at mean accuracy of 1.28±0.87 mm for the synthetic phantoms and of 1.74±0.89 mm for the human cadavers. CONCLUSION: The results and experiments demonstrate the feasibility of the proposed system in a pre-clinical setting. This work is complementary to previous work, encouraging further exploration of the potential of this technology in in vivo studies.

Association between Meteorological Factors and Outpatient Visits for Herpes Zoster in Hefei, China: A Time-Series Analysis.

This study sought to investigate the relationship between meteorological factors and outpatient visits for herpes zoster. In this time-series analysis, we used data from two major hospitals in Hefei, collected between 2015 and 2019, to evaluate the impact of meteorological factors on the risk of herpes zoster. After controlling for confounders, we adopted a distributed lag nonlinear model to probe the relationship between meteorological factors and outpatient visits for herpes zoster. The analysis was stratified according to age (<40 years, ≥40 years) and sex (male, female). A total of 43,547 cases of herpes zoster were reported, and compared with the median value, a high temperature and high relative humidity had a significant risk effect on the incidence of herpes zoster. The maximum harmful effect of high temperature on herpes zoster occurred on the lag0 (RR: 1.027, 95% CI: 1.002-1.053) and further declined over the following days. The cumulative effect increased with the extension of lag days, and the cumulative RR was the largest on the sixth day of lag (RR1.031, 95% CI: 1.006-1.056) when the relative humidity was 85.7% (77.0% as the reference). The stratified analysis results reveal that females and the elderly (≥40 years) were more susceptible to temperature and relative humidity. This study shows that high-temperatures may lead to herpes zoster, indicating that those infected with varicella zoster virus need to take measures over the course of several days when not exposed to the best appropriate temperature conditions.

Short-term effect of ambient temperature and ambient temperature changes on the risk of warts outpatient visits in Hefei, China: a retrospective time-series study.

Concerns are growing about the adverse health effects of ambient temperature and ambient temperature changes. However, the association between ambient temperature and ambient temperature changes on the risk of warts outpatient visits is poorly understood. Our study used the distributed lag non-linear model (DLNM) aimed to evaluate the association between ambient temperature, ambient temperature changes (including temperature change between neighboring days (TCN) and diurnal temperature range (DTR)), and warts outpatient visits. We also performed subgroup analyses in order to find susceptible populations by gender and age groups. The maximum relative risk (RR) of low ambient temperature (0 °C) for warts outpatient visits was 1.117 (95% CI: 1.041-1.198, lag 04 days), and the maximum RR of high ambient temperature (32 °C) for warts outpatient visits was 1.318 (95% CI: 1.083-1.605, lag 07 days). The large temperature drop (TCN = - 3 °C) decreased the risk of warts visits, with the lowest RR value at the cumulative exposure of lag 7 days (RR = 0.888, 95% CI: 0.822-0.959), and the large temperature rise (TCN = 2 °C) increased the risk of warts visits, with the highest RR value at the cumulative exposure of lag 7 days (RR = 1.080, 95% CI: 1.022-1.142). Overall, both low and high ambient temperatures and large temperature rise can increase the risk of warts visits, while large temperature drop is a protective factor for warts visits. However, we did not find any association between DTR and warts visits. Furthermore, subgroup analyses showed that males and the young (0-17 years old) were more sensitive to low and high ambient temperatures, and the elderly (≥ 65 years old) were more susceptible to TCN. The results may provide valuable evidence for reducing the disease burden of warts in the future.

Effect of Cytochrome P450 7A1 (CYP7A1) Polymorphism on Lipid Responses to Simvastatin Treatment.

BACKGROUND: Identifying patients with high risk of low response to statin therapy is important for optimization of lipid-lowering therapy. Cholesterol 7α-hydroxylase, a rate-limiting enzyme encoded by cytochrome P450 7A1 (CYP7A1) gene, is considered to be associated with statin efficacy. This study aimed to investigate the association between a novel CYP7A1 single nucleotide polymorphism rs3824260 and statin treatment response for hypercholesteremic patients in Chinese Han population. METHODS: A total of 336 subjects were prescribed with simvastatin for 12 weeks after enrollment. Plasma lipid parameters were measured at enrollment and after 12-week simvastatin treatment separately. Subjects were classified into high- and low-response groups depending on their total cholesterol, low-density lipoprotein cholesterol (LDL-C) and TG changes and increase or reduction groups according to their high-density lipoprotein cholesterol (HDL-C) levels changing after simvastatin treatment. The CYP7A1 rs3824260 was genotyped from blood samples with a SNaPshot assay. RESULTS: At baseline, the LDL-C level and TG level were significantly higher in the AA genotype, while the HDL-C level was significantly higher in the GG genotype of CYP7A1 rs3824260. Patients carrying AA genotype are at an increased risk of low response for LDL-C reduction (odds ratio = 2.295, 95% confidence interval = 1.164-4.524, P = 0.016). Furthermore, the GG genotype of rs3824260 was significantly associated with a high risk of HDL-C reduction response after simvastatin therapy (odds ratio = 2.240, 95% confidence interval = 1.137-4.413, P = 0.025). CONCLUSIONS: The CYP7A1 gene polymorphism rs3824260 is related to inappropriate response of simvastatin treatment for hypercholesterolemia patients in Chinese Han population.

Association of ABCC2 polymorphism and gender with high-density lipoprotein cholesterol response to simvastatin.

AIM: The clinical benefits of lipid-lowering therapy with statins are widely recognized. However, the lipid-lowering efficacy of statins shows significant differences between individuals. ABCC2 has been demonstrated to contribute to the transmembrane transport of the substrate compounds. The ABCC2 SNPs may be important factors that affect individual differences in clinical drug response. The aim of this study was to evaluate the association of rs717620 of ABCC2 with treatment response to simvastatin in a Chinese Han population. METHODS: A total of 318 subjects were medicated with simvastatin 20 mg/day for 12 weeks after enrollment. Venous blood was obtained before and after simvastatin treatment for measurement of blood lipid profile. Subjects were classified into high-response and low-response groups depending on whether their lipid profile change was higher or lower than median change values. The ABCC2 SNP rs717620 was genotyped from blood samples with a snapshot assay. RESULTS: A total of 12 weeks of treatment with simvastatin significantly decreased low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TGs) and significantly increased high-density lipoprotein cholesterol (HDL-C; p < 0.05). In multivariate analysis, there were no significant genetic effects of SNP rs717620 on the incidence of high- or low-response patients among TC, TG and LDL-C groups. However, rs717620 A-allele and female gender are significantly associated with the risk of low-response of HDL-C elevation after simvastatin treatment. CONCLUSION: ABCC2 rs717620 and female gender may be related to the low-effect of simvastatin treatment on the HDL-C level in the Chinese Han population. Female Chinese patients with hyperlipidemia carrying rs717620 GA/AA genotypes might have reduced benefit from simvastatin treatment.

Adipose Triglyceride Lipase Gene Polymorphisms is Not Associated with Free Fatty Acid Levels in Chinese Han Population.

BACKGROUND: Elevated levels of free fatty acids (FFAs) play a role in the pathogenesis of insulin resistance and atherosclerosis. Adipose triglyceride lipase (also defined as patatin-like phospholipase domain containing 2 or PNPLA2) has been demonstrated to contribute to the release of FFA. The aim of this study was to investigate the association of PNPLA2 gene variations with FFA levels in healthy Chinese Han population. METHODS: Single-nucleotide polymorphisms of PNPLA2 were genotyped using TaqMan method to perform association studies with serum level of FFA and other lipid parameters in 1765 subjects among healthy Chinese Han population. All the subjects were divided into two groups: normal FFAs group (FFAs ≤0.88 mmol/L) and high FFAs group (FFAs >0.88 mmol/L). RESULTS: Neither rs7925131 nor rs7942159 was significantly associated with FFA level. We observed no difference in the genotype frequency of rs7925131 or rs7942159 between the normal FFA group and the high FFA group. CONCLUSIONS: Our results do not support an association of rs7925131 or rs7942159 with the FFA levels among the Chinese Han population.

A Variant in ADIPOR2 Is Associated with Increased Free Fatty Acid Levels in Chinese Population.

BACKGROUND: Elevated free fatty acids (FFAs) are thought to play an important role in the development of insulin resistance. Adiponectin is an adipose tissue-secreted protein known for its effects on the stimulation of fatty acid oxidation. The aim of this study was to investigate the association of adiponectin receptor 2 gene variations with FFAs levels in subjects with normal fasting glucose levels in Chinese Han population. METHODS: Four common single nucleotide polymorphisms of ADIPOR2 were genotyped using the TaqMan method to perform association studies with metabolic parameters in 1819 subjects among Chinese Han population. All the subjects were divided into two groups: normal FFAs group (FFAs ≤0.88 mmol/L) and high FFAs group (FFAs >0.88 mmol/L). RESULTS: There was a significant association of rs2370055 with higher FFA levels in major T-allele carriers (P = 0.000). There was a significant difference in the distribution of genotypes of polymorphism rs2370055 between normal and high FFA groups. The frequencies of TT and CT genotypes are significantly higher in subjects with high FFA level than those in the normal FFAs group (P = 0.013 and P = 0.004, respectively). After adjustment for age, sex, body mass index, triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoproteincholesterol, the TT and CT genotypes are both independent risk factors for high FFAs level. CONCLUSIONS: Our findings suggest that variants of ADIPOR2 could be a determinant for higher FFA levels, and among Chinese Han population, carriers of the CT and TT genotypes for rs2370055 even with normal glucose levels may have significantly higher insulin resistance susceptibility.

[The relationship between the level of circulating endothelial progenitor cells CD34+; and carotid artery arteriosclerosis in youth and middle aged patients with essential hypertension].

OBJECTIVE: To explore the relationship between the level of circulating endothelial progenitor cells (EPCs) CD34+ with the Framingham cardiovascular risk factors, or with the carotid artery intima-media thickness (IMT), and to evaluate the value of circulating EPCs CD34+ level as a cytological marker of early vascular lesion in youth and middle aged essential hypertension (EH) patients. METHODS: A total of 62 patients with EH aged between 25 to 45 were enrolled as study group and 20 healthy people were enrolled as control group. EH patients were stratified with cardiovascular risk factors according to Framingham risk factors score into low-risk group with 18 cases, mid-risk group with 14 cases, high-risk group with 17 cases, and extremely high-risk group with 13 cases. The level of circulating EPCs CD34+, carotid artery IMT were respectively measured. The relationship between the level of circulating EPCs CD34+ and Framingham cardiovascular risk factors score, carotid artery IMT was analyzed. RESULTS: The level of circulating EPCs CD34+ was gradually decreased with an increase of the Framingham risk factors score in each hypertensive subgroup [low-risk group: (0.12+/-0.02)%, mid-risk group: (0.07+/-0.03)%, high-risk group: (0.04+/-0.03)%, extremely high-risk group: (0.01+/-0.01)%], and they were significantly lower than that in control group [(0.15+/-0.03)%], and there was a significant difference among hypertensive subgroups (P<0.05 or P<0.01). Carotid artery IMT was significantly thicker among hypertensive subgroups [low- risk group: (0.80+/-0.07) mm, mid-risk group: (1.11+/-0.08) mm, high-risk group: (1.26+/-0.10) mm, extremely high-risk group: (1.45+/-0.09) mm], and there was a significant difference between each hypertensive group and that of control group [(0.73+/-0.08) mm, all P<0.01]. There was also statistical significance among hypertensive subgroups (P<0.05 or P<0.01). There was a negative correlation between the level of circulating EPCs CD34+ and Framingham risk factors score (r=-0.875, P<0.01), and also a negative correlation with carotid artery IMT (r=-0.852, P<0.01). CONCLUSION: There was a significant correlation between the level of circulating EPCs CD34+ with Framingham risk factors score and also carotid artery IMT in EH patients. Circulating EPCs CD34+ could be a cytological marker of early vascular lesion in hypertension patients.