Sterol 14alpha-demethylase (CYP51), the most widely distributed member of the P450 superfamily, is the key enzyme in sterol biosynthesis pathway. CYP51 is not only an important model for fundamental P450 structure/function studies, but also an important target protein of cholesterol-lowering agents, antifungal drugs and herbicides. This article reviewed the research advances in CYP51 at various aspects, including sequence characteristics, physiological roles, catalytic properties in vitro, protein structure, structure-function relationships and inhibition of CYP51. The problems remained in current research and designations of CYP51 inhibitors are also discussed.
Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System ; genetics ; physiology ; Mutagenesis, Site-Directed ; Sequence Analysis, Protein ; Sterol 14-Demethylase

Objective:To evaluate the efficacy of balloon pulmonary angioplasty (BPA) in chronic thromboembolic pulmonary hypertension (CTEPH) using 99Tc m-macroaggregated albumin (MAA) pulmonary perfusion tomography imaging. Methods:Twenty-five patients (4 males, 21 females; age (56.5±12.3) years) with CTEPH who underwent BPA from January 2017 to April 2020 in Beijing Chaoyang Hospital, Capital Medical University were enrolled retrospectively. Effect of BPA on the improvement of pulmonary lobe/pulmonary segment perfusion was analyzed, and the proportions of improved and unimproved pulmonary lobe/pulmonary segment perfusion by BPA were calculated. The percentages of perfusion defect scores (PPDs%) of lung perfusion tomography imaging before BPA and after 4-6 times BPA were compared and analyzed (paired t test). The correlations between PPDs% and mean pulmonary artery pressure (mPAP) before BPA and after BPA were analyzed respectively, and the correlation between decreased percentage of PPDs% and decreased percentage of mPAP after BPA were also analyzed (Pearson correlation analysis). Results:Among 150 lobes of 25 patients, 96.00%(144/150) lobes showed perfusion abnormalities before BPA. After BPA, 11.11%(16/144) showed complete improvement, 57.64%(83/144) showed partial improvement, and 31.25%(45/144) showed no improvement. Among 450 pulmonary segments of 25 patients, 62.44%(281/450) showed perfusion abnormalities before BPA. After BPA, 30.60%(86/281), 37.37%(105/281), 32.03%(90/281) showed complete, partial and no improvement, respectively. The post-BPA PPDs% was significantly lower than that of pre-BPA ((39.08±10.88)% vs (57.88±10.46)%; t=10.40, P<0.001). The post-BPA mPAP was significantly lower than that of pre-BPA ((32.36±10.57) vs (49.08±10.23) mmHg; 1 mmHg=0.133 kPa; t=10.25, P<0.001). There was no significant correlation between PPDs% and mPAP either before BPA ( r=0.01, P=0.953) or after BPA ( r=0.27, P=0.199), but there was a positive correlation between the changes of PPDs% and mPAP ( r=0.40, P=0.045). Conclusions:BPA can significantly improve the pulmonary perfusion and reduce mPAP in CTEPH patients. Pulmonary perfusion tomography imaging can be used to evaluate the efficacy of BPA in CTEPH.

Objectives:To investigate the association between normal-weight central obesity with new-onset cardiovascular disease and all-cause mortality risk. Methods:A prospective cohort study was conducted,selecting a total of 93885 participants from the Kailuan Study who had their first physical examination in 2006-2007.According to waist circumference (central obesity:male waist circumference ≥90 cm,female waist circumference ≥85 cm;no central obesity:male waist circumference<90 cm,female waist circumference<85 cm) and body mass index (BMI,normal weight:18.5 kg/m2≤BMI<24.0 kg/m2;overweight/obesity:BMI ≥24.0 kg/m2),the participants were divided into 4 groups:normal weight no central obesity group (G1 group),normal weight central obesity group (G2 group),overweight/obesity no central obesity group (G3 group) and overweight/central obesity group (G4 group);Using the Kaplan-Meier method,the cumulative incidence of new-onset cardiovascular diseases (including hemorrhagic stroke,ischemic stroke and myocardial infarction) and all-cause mortality in different groups was calculated,and the Log-rank test was used for intergroup comparisons.Furthermore,the associations between the different groups and the risk of new-onset cardiovascular diseases and all-cause mortality were analyzed using the multivariate Cox proportional hazard regression model. Results:After a median follow-up of 14.97 (14.55,15.17) years,the cumulative incidence of new-onset cardiovascular diseases in G1 group,G2 group,G3 group and G4 group was 7.62％,10.84％,8.67％,12.91％ respectively (log-rank P<0.05) and the cumulative incidence of all-cause mortality was 12.83％,19.72％,10.65％,16.33％ respectively (log-rank P<0.01).After adjusting for confounding factors,Cox regression analysis showed that the HR (95％CI) of new-onset cardiovascular diseases in G2 group,G3 group and G4 group were 1.14 (1.04-1.25),1.07 (1.01-1.14),1.27 (1.21-1.34),respectively compared with G1 group (all P<0.05).The HR (95％CI) of all-cause mortality were 1.06 (1.00-1.14),0.90 (0.85-0.95),0.97 (0.93-1.01) compared with G1 group,and P values were 0.07,<0.01,0.15,respectively.The results of sensitivity analysis were consistent with the above major studies after excluding overweight/obesity and cancer participants during follow-up. Conclusions:Normal-weight central obesity increases the risk of new-onset cardiovascular diseases and all-cause mortality.

Objective To explore the characteristics and significance of functional connectivity (FC) of affective network (AN) in patients with postpartum depression (PPD) under resting state. Methods A total of 23 patients with PPD (PPD group) and 28 healthy postpartum women (control group) were examined using resting-state fMRI. As two critical nodes of AN, amygdala (AMYG) and subgenual anterior cingulate cortex (sgACC) were selected as the regions of interest (ROI) to analyze the differences of functional connectivity strength (FCS) of two regions from other brain regions between two groups, followed by Pearson correlation analysis on the abnormal FCS and the Edinburgh postnatal depression scale (EPDS) score in PPD group. Results Compared to the control group, the patients in PPD group showed the extensively reduced FCS (P<0.05, Alphasim correction) between AMYG and frontal cortex, temporal cortex, hippocampus, cerebellum and orbitofrontal cortex, while there were enhanced FCS (P<0.05, Alphasim correction) between sgACC and parietal cortex, occipital cortex, thalamus, superior temporal gyrus and cingulate cortex. Moreover, in PPD group, the reduced FCS between left AMYG and left medial orbitofrontal cortex was negatively correlated with EPDS scores (r=-0.62, P=0.02). Conclusion Patients with PPD have dysfunctional connectivity of AN in multiple brain regions. The weaker FCS between left amygdala and left medial orbitofrontal cortex is, the more severe depression. The dysfunctional connectivity of AN may provide an effective mechanism-based biomarker underlying PPD.

Objective:To explore suitable strategies for atrial 18F-FDG PET/CT imaging and analyze the characteristics of abnormal atrial uptake in patients with atrial fibrillation(AF). Methods:From August 2017 to August 2018, 69 AF patients (43 males, 26 females, age (64±11) years) in Beijing Chaoyang Hospital were prospectively enrolled and underwent dual-phase 18F-FDG PET/CT imaging (60 and 120 min postinjection). Additionally, 10 healthy controls (3 males, 7 females, age (66±4) years) were prospectively enrolled and underwent 18F-FDG PET/CT imaging (60 min postinjection). A comprehensive strategy recommended by the Society of Nuclear Medicine and Molecular Imaging/American Society of Nuclear Cardiology/Society of Cardiovascular Computed Tomography (SNMMI/ASNC/SCCT) guideline was followed to suppress myocardial uptake. Image analysis: (1) 18F-FDG uptake of left ventricle was qualitatively analyzed and classified into 3 levels: grade 0, the activity of blood pool exceeded or was equal to myocardial activity; grade 1, myocardial activity was mildly higher than blood pool activity; grade 2, myocardial activity was obviously higher than blood pool activity. 18F-FDG uptake in the left atrium(LA), left atrial appendage (LAA) and right atrium (RA) higher than that in blood pool were defined as abnormal. Paired χ2 test was used to compare the rates of abnormal uptake in atrial structures between two phases. (2) Quantitative analysis: 18F-FDG uptake in all atrial structures were quantitatively analyzed by measuring SUV max, and left atrial cavity and right atrial cavity were quantitatively analyzed by measuring SUV mean. The target to background ratio (TBR) was calculated. Differences of TBR between two phases were analyzed by Wilcoxon signed rank test. Differences of 18F-FDG uptake in atrial structures between patients with AF and healthy controls were analyzed by Mann-Whitney U test and χ2 test. Results:Most subjects (84.8%, 67/79) achieved sufficient myocardial suppression. In one patient, the interpretation of LAA was affected by left ventricle uptake. The incidence of abnormal uptake of LA, LAA and RA in delayed phase were higher than those in early phase, but only the difference of LAA was significantly different (27.9%(19/68) vs 42.6%(29/68); χ2=8.10, P=0.020). TBR of LA, LAA and RA in delayed phase were all significantly higher than those in early phase (LA: 1.1 (1.0, 1.3) vs 1.1 (1.0, 1.2); LAA: 1.2 (1.0, 1.5) vs 1.0 (0.9, 1.2); RA: 1.4 (1.1, 1.9) vs 1.3 (1.0, 1.5); z values: from -6.81 to -3.42, all P<0.05). There were 87.0%(60/69) of AF patients with abnormal atrial FDG accumulation, which was significantly higher than that of the control group (0/10; χ2=31.50, P<0.001). In LAA and RA, the incidences of abnormal accumulation were significantly higher in AF than those in the control group (LAA: 30.4%(21/69) vs 0 (0/10); χ2=4.10, P=0.042; RA: 53.6%(37/69) and 0 (0/10); χ2=8.00, P=0.001). Conclusions:Using the method recommended by the SNMMI/ASNC/SCCT guideline to suppress the physiological uptake of the left ventricle and appropriately extending the interval is conducive to observing the abnormal 18F-FDG uptake in the atrium. The uptake of 18F-FDG in the atrium of patients with AF is increased.

Objective:To evaluate the MRI manifestations of condylar bone regeneration after disc reduction and suture for anterior disc displacement without reduction (ADDWoR) patients and to analyze the relevant factors affecting bone regeneration.Methods:A total of 61 patients of 75 joints with ADDWoR who attended the Department of Maxillofacial Surgery of the Affiliated Hospital of Stomatology of Nanjing Medical University from April 2020 to December 2021 were enrolled in the study. The characteristics of MRI condylar bone regeneration were analyzed before and after surgery (follow-up for 6 months or more), and logistic regression analysis was performed on the influencing factors of bone regeneration.Results:The new bone formation of the condyle was found in 28 patients, with age of (20.2±4.9) years. However, there were 33 patients that had no condylar bone regeneration, with age of (41.9±17.5) years. A total of 35 joints in this study were found new bone formation. There were 16 joints (45.7%) had new bone formation on the posterior slope of the condyle, 10 joints (28.6%) around the condyle, 6 joints (17.1%) on the anterior slope of the condyle, and only 3 joints (8.6%) on the top of the condyle. Multivariate logistic regression analysis showed that age, preoperative disc length and degree of condylar bone resorption correlated with postoperative condylar bone regeneration( P<0.05). Patients younger than 30 years with non-shortened preoperative disc length and less condylar bone resorption have a higher probability of new bone formation. Conclusions:The condyle has bone regeneration capacity after correcting the abnormal relationship between disc and condyle, and young age, non-shortened preoperative disc length and less condylar bone resorption are conducive to postoperative condylar bone regeneration.