Hereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST, inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.C748T, p.R250W) and KIF3C (c.G1229A, p.R410H) genes within the GINGF3 locus related to HGF. Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo. ZNF513, a transcription factor, binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts. Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. In addition, we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1. Moreover, the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels. ZNF513 combined with KIF3C regulates gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways. In summary, these results demonstrate ZNF513 + KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.
Animals ; Humans ; Mice ; Fibromatosis, Gingival/pathology* ; Gingiva ; Kinesins/genetics* ; Mutation/genetics* ; Phosphatidylinositol 3-Kinases/genetics*

Objective:To assess the clinical and imaging features of SMARCB1-deficient sinonasal carcinoma.Methods:Form January 2016 to November 2021, the clinical data and pretreatment imaging findings of 16 cases with pathologically proven SMARCB1-de?cient sinonasal carcinomas were analyzed retrospectively in Beijing Tongren Hospital, Capital Medical University. Immunohistochemistry for SMARCB1 showed loss of the protein in the tumor nuclie. Clinical and imaging features, including tumor location, TNM stage, size, density of CT, bone change, MRI signal intensity, enhancement pattern, type of time-intensity curve (TIC) of dynamic contrast enhanced MRI (DCE-MRI), apparent diffusion coefficient (ADC) value and diffusion weighted imaging (DWI) were evaluated. For 14 cases, correlation of the ADC value and Ki-67 index was subsequently evaluated with Pearson correlation analysis.Results:For the 16 cases SMARCB1-deficient sinonasal carcinomas, clinical stage of T4 was 12 cases and T3 was 4 cases. The location included ethmoid sinus ( n=4), nasal cavity only ( n=1), both nasal cavity and ethmoid ( n=8), ethmoid and maxillary sinus ( n=1), ethmoid and frontal sinus ( n=1), ethmoid and sphenoid sinus ( n=1). The tumor size was (4.5±1.2) cm. Iso-attenuated of CT images was showed in 13 cases and heterogeneous with necrosis was showed in 3 cases. Focal bone erosion was found in 13 cases and extensive bone destruction was found in 3 cases. Compared with adjacent muscles, T 1WI of all 16 cases showed isointense, with focal hypointense in 3 cases. On T 2WI, the tumor was graded as isointense in 9 cases, hyperintense in 7 cases, with lower inner septal in 6 cases. Enhancement was graded as mild in 11 cases, moderate in 5 cases.MRI Enhancement images showed mild enhancement in 11 cases, moderate enhancement in 5 cases, heterogeneous enhancement in 6 cases, and homogeneous enhancement in 10 cases. For DCE-MRI of 14 cases, there were 10 cases of Ⅲ type and 4 cases of Ⅱ type of the TIC. The ADC value of 14 cases was (1.02±0.27)×10 -3 mm 2/s. The Ki-67 index was 48%±21%. No correlation was observed between Ki-67 index and ADC value ( r=-0.38, P=0.183). Conclusions:SMARCB1-deficient carcinomas are mostly centered in the nasal and ethmoid region of anatomic distribution. Tendency to be infiltrative the adjacent bone structure with invasive bone reaction, mild to moderate heterogeneous enhancement, T 2WI with lower inner septal, and Ⅲ types of TIC are certain suggestive imaging features of the entity.

Objective:To assess the clinical and imaging features of NUT gene-related sinonasal carcinomas (NUT midline carcinome).Methods:The clinical data and pretreatment imaging findings of 5 cases with pathologically proven NUT sinonasal carcinomas were analyzed retrospectively in Beijing Tongren Hospital, Capital Medical University from January 2016 to December 2020. Of 5 cases, the tumors affected 4 females and 1 male with an age range of 15 to 48 years (median 19 years). Clinical data of all cases were available before surgery with both CT and MR examination. Tumor location, CT density, boney change, calcification, tumor size, T 1WI, T 2WI and diffusion weighted imaging (DWI) signal intensity, appearance diffusion coefficient (ADC), type of time intensity curve (TIC) of dynamic contrast-enhanced (DCE)-MRI were evaluated. Results:All five cases belonged to T4 stage of the clinic TNM system. The locations were nasal cavity ethmoid, sphenoid and maxillary sinus ( n=1), nasal and maxillary sinus ( n=1), nasal cavity and ethmoid sinus ( n=3). Iso-attenuated in 3 cases, heterogeneous with local necrosis in 2 cases, and heterogeneous with calcification in 3 cases on CT imaging. Bone erosion was found in 4 cases, and bone erosion with destruction in 1 case. The tumor sizes ranged from 4.2 to 4.9 cm (median 4.5 cm) on MR axial imaging. On T 1WI, 5 cases showed isointense compared with adjacent temporal muscles, with focal hypointense in 2 cases. On T 2WI, the tumor was graded as isointense in 3 cases, and hyperintense in 2 cases. Heterogeneous enhancement in all cases with mild in 3 cases, and moderate in 2 cases on postcontrast MR imaging. On DCE-MRI of 5 cases, there were 3 cases of type Ⅲ (washout-shaped curves), and 2 cases of type Ⅱ of the TIC (plateau-shaped curves). The range of ADC values was from 0.63×10 -3 to 1.17×10 -3 mm 2/s, and median ADC value was 0.84×10 -3 mm 2/s, of 5 cases with varying degrees of high signal on DWI. The Ki-67 index ranged from 30% to 80% of the tumor. An immunohistochemical study showed that the tumor cells of 5 cases were all positive for both NUT and INI-1 genes. One case was performed with biopsy and followed by chemotherapy, four cases were performed with surgery, combined with the following chemotherapy, and one also was implemented with radiation therapy. The follow-up time was 7-16 months. Five cases were all alive during the follow-up. Conclusions:The NUT midline sinonasal tract carcinoma is a rare, gene-related solid malignant tumor. The tumor is more commonly seen in young patients, mostly centered in the nasal and ethmoid region with invasive growth, more calcification on CT, and heterogeneous enhancement on MRI. These findings are some characteristics of the tumor.

Objective:To compare the diagnostic value of three quantitative evaluation methods based on three-dimensional rapid fluid attenuation inversion recovery sequence (3D-FLAIR) vein-enhanced labyrinth images in endolymphatic hydrops.Methods:From October 2017 to April 2019, a retrospective study was conducted on 86 patients with unilateral otogenic vertigo who were admitted to Beijing Tongren Hospital, Capital Medical University. MRI was performed 8 h after the single-dose Gd-DTPA intravenously injection in all patients. Three evaluation methods were used to calculate the ratio of the endolymphatic area to the total lymphatic area, the ratio of the saccule to utricle area, and the ratio of the endolymphatic volume to the total lymphatic volume, respectively. The paired t test was used to compare the three ratios between the affected and healthy ears. With clinical diagnosis as the gold standard, the receiver operating characteristic (ROC) curve analysis was used to analyze the efficacy of three methods in diagnosing endolymphatic hydrops. Results:Totally 65 cases were finally diagnosed endolymphatic hydrops clinically. There were statistically significant differences of all the 3 ratios between the affected and healthy ears ( t=9.93, 7.22, 8.20, all P<0.001). The ROC curve showed that the area under the curve (AUC) of endolymph/total lymph area ratio, saccule/utricle area ratio, endolymph/total lymph volume ratio for diagnosis of endolymphatic hydrops were 0.882, 0.768, 0.884 (all P<0.001). And there were no significant differences between each paired AUCs (all P>0.05). Conclusions:All three methods of endolymph/total lymph area ratio, saccule/utricle area ratio, endolymph/total lymph volume ratio can quantitatively evaluate endolymphatic hydrops. The endolymphatic/total lymphatic area ratio method is still the most convenient method at present.

Objective:To investigate the effect of different scanning modes, detector width and location in detector on high and low contrast resolution of wide-detector CT image.Methods:The Catphan600 phantom with high and low contrast resolution modules was scanned with GE Revolution CT at the same CTDI vol. The scans were performed with the detector widths of 40, 80 and 160 mm for sequential scanning mode and with the detector width/pitch combinations of 40 mm/0.516, 40 mm/0.984, 80 mm/0.508 and 80 mm/0.992 for spiral scanning mode. The resolution modules were placed at the adjacent region between two sequential scans, central and foot side edge in the longitudinal scanning range seperately. The subjective evaluation of the high and low contrast resolution was performed by two radiologists. Results:The high contrast resolution was 8 LP/cm at adjacent region between two sequential scans with the detector width of 80 mm or 160 mm in sequential scanning mode, and at the pitch of 0.5 in spiral scanning mode, while it was 7 LP/cm for the rest of detector combinations. The distinguishable diameter was 3 mm at 1% low contrast resolution at foot side edge with the detector widths of 80 mm or 160 mm in the sequential scanning mode, and it was 2 mm for all the other conditions. The distinguishable diameter was 2 mm at 1% low contrast resolution with the detector width of 40 mm and pitch 0.516 in the spiral scanning mode and it was worse with the wider detector and larger pitch.Conclusions:For the wide-detector CT, scanning mode, detector width, location in detector and pitches will affect the high and low contrast resolution to some degree. Appropriate selection should be done according to actual needs in clinical practice.

Objective To identify the potential prognostic biomarkers of the immune-related genes signature for patients with hepatocellular carcinoma (HCC). Methods Original HCC data were downloaded from TCGA, and the immune activity of each sample was calculated by ssGSEA. HCC samples were divided into high and low immune cell infiltration groups by "GSVA" package and "hclust" package. The ESTIMATE algorithm scored the tumor microenvironment in each HCC sample. The "limma" package and Venn diagram identified effective immune-related genes. Univariate Cox, Lasso regression and multivariate Cox regression analyses were used to explore key genes. The "rms" package was used to create nomograms and draw calibration curves. Results Compared with the high immune cell infiltration group, the tumor purity of the samples in the low immune cell infiltration group was higher, the immune score, ESTIMATE score and stromal score were lower. In the high immune cell infiltration group, the immune components were more abundant, and the expression levels of TIGIT, PD-L1, PD-1, LAG3, TIM-3, CTLA4 and HLA family were higher. Multivariate Cox regression analysis showed that four immune-related genes (S100A9, HMOX1, IL18RAP and FCER1G) were used to construct the prognosis model. Compared with other clinical features, the risk score of this prognostic model was recognized as an independent prognostic factor. Conclusion This study identified the immune-related core genes which may be used in targeted therapy and immunotherapy of HCC.

Objective:To explore the clinical application value of each sequence by analyzing the characteristics of labyrinthine signal on MRI in patients with unilateral sudden deafness.Methods:Totally 52 patients of unilateral sudden deafness with inner ear MRI were analyzed retrospectively at Beijing Tongren Hospital, Capital Medical University from January 2016 to July 2019, all of which could find abnormalities in the labyrinth, including 17 cases of plain scan and 35 cases of enhanced scan, with sequences including plain T 1WI, enhanced T 1WI, plain and enhanced delayed 3D fluid attenuation inversion recovery (3D-FLAIR). The affected labyrinthine signal characteristics of each sequence were analyzed and the involvement sites were judged. The ability of each sequence to show labyrinthine abnormal signal was evaluated and scored. The Friedman test and Wilcoxon signed rank sum test were used to compare the subjective scores of the ability to show labyrinthine high signal in different sequences in plain and enhanced patients, respectively. Fisher′s exact probability method was used to analyze the relationship between the affected sites and the recovery of hearing, tinnitus and vertigo symptoms. Results:Fifty-two patients (100%, 52/52) showed labyrinthine high signal on T 1WI, 8 (15.4%, 8/52) showed higher signal and 3 (5.8%, 3/52) showed low signal on T 2WI. Thirty-five (100%, 35/35) showed high signal on enhanced T 1WI, among which 27 had enhancement (77.1%, 27/35). Fifty-two (100%, 52/52) showed significant high signal of the affected labyrinth on 3D-FLAIR (17 plain scan, 35 enhanced scan). The scores were 2 (2, 2), 3 (2, 3), 3 (3, 4) and 4 (4, 4) of T 1WI, enhanced T 1WI, plain and enhanced 3D-FLAIR respectively. The overall difference in subjective scores of plain T 1WI, enhanced T 1WI and enhanced 3D-FLAIR in enhanced patients was statistically significant (χ2=64.528, P<0.001), and the comparison between the two was statistically different (all corrected P<0.05). The plain 3D-FLAIR score was higher than the plain T 1WI in patients with a statistically significant difference ( Z=-3.729, P<0.001). Twenty-seven cases (51.9%, 27/52) exhibited high signal at the ampulla of semicircular canals, with a statistically significant difference in the distribution of hearing recovery or not ( P=0.001). Conclusions:Both T 1WI and 3D-FLAIR sequences can effectively identify the labyrinthine high signal, but the latter was better than the former of its ability to display, especially delayed enhanced 3D-FLAIR. The high signal at the ampulla of semicircular canals was a characteristic predictor of non-recovery of hearing.

Objective To explore the effects on image quality and dose reduction to the lens when using bismuth shielding in head and neck MSCT.Methods The standard phantom and the cadaveric head with none,1,2 and 3 layers of bismuth shielding were scanned with protocols of brain,temporal bone and paranasal sinuses using a 16-MDCT scanner.The organ dose to the lens in each scanning was measured with thermoluminescence dosimeters(TLD).The above scanning with sinus protocol was repeated with a sponge with thickness of 5,10,15 and 20 mm placed between the shielding and phantom/head.The CT attenuation of phantom with the distance of 2,4,6 and 8 cm to shielding were measured.The image quality was subjectively evaluated by 2 physicians.Results The organ doses of the lens with protocols of brain,temporal bone and sinuses were 24.31,27.60 and 20.01 mGy,respectively.The doses were decreased significantly when using bismuth shielding.With the increase of the shield gap,the degree of dose reduction was reduced,but the increasing degree of CT attenuation significantly reduced.Using 2-layer and 3-layer bismuth shield in brain and temporal bone CT scan,the radiation doses were reduced by 47.1％ and 59.1％,respectively while maintaining the diagnostic image quality.Using 1-layer shield without gap and 2-layer shield with 1.5 cm gap in sinus CT,the radiation doses were reduced by 31.5％ and 34.5％,respectively.Conclusions Reasonable usage of bismuth shielding can effectively reduce the radiation dose to the lens of eye in head and neck MSCT.

Objective To investigate the influence of tube voltage on image quality and radiation dosage to subjects in chest digital radiography (DR).Methods An adult chest phantom was exposed in the range of 80-130 kV with the interval of 10 kV and the automatic exposure control (AEC) setting was selected from-4 to 4.The entrance skin dose (ESD) of the phantom was measured,and the relative noise,contrast-to-noise ratio (CNR) and the effective dose of each exposure was calculated.Results The ESD was (0.062 9 ±0.027 4) mGy,and the effective dose was (0.012 7 ±0.004 5) mSv.The effective dose increased linearly with the ESD,and there was a positive correlation (r =0.912,P ＜ 0.01).When the tube voltage was held constant,the relative noise decreased as the effective dose increased (r =-0.967,-0.969,-0.968,-0.969,-0.968,-0.970,P ＜ 0.01).The CNR increased with the effective dose increasing under the same tube voltage(r =0.987,0.987,0.986,0.987,0.988,0.989,P ＜0.01).The ESD and effective dose decreased as the kV values increased under the same AEC,and the degree of decrease could be up to 50％ and 20％.The relative noise decreased as the kV values increased under the same AEC,and the degree of decrease could be up to 23％.The CNR values increased up to 8％.Conclusions The use of higher kVp in chest digital radiography can reduce the radiation dose to some extent

Objective To explore the influence on image quality and the reduction of radiation dose to eye lens when using bismuth shielding in sinus MDCT.Methods The standard water phantom was scanned using clinical scanning protocols of sinus in 16-MDCT,and the images were acquired with none,1 layer,2 layers and 3 layers of bismuth shielding severally.Using the above protocol,the cadaveric head was scanned with no shield,1,2 and 3 layers of bismuth shielding material covered on both eyes,and the organ dose to eye lens in each scanning was measured with thermoluminescence dosimeter (TLD).The sponge with the thick of 0.5,1.0,1.5,2.0 cm was placed between the shielding material and the surface of subjects separately and the radiation doses to eye lens was measured with sinus scanning conditions in the same way.The CT values of phantom with the distances of 2.0,4.0,6.0 and 8.0 cm to shield material were measured.The influence of bismuth artifacts on anatomic structures was evaluated as well.Results The organ doses to the eye lens in the sinus clinical CT were 20.0 mGy.Doses decreased significantly to 13.7,10.9 and 9.4 mGy separately when using 3 types of bismuth shielding thickness.With different thicknesses of shielding material,the greater the shield gap,the smaller the degree of reduction of organ dose,but the increasment of CT value was significantly reduced.Using 1-layer shield no gap and 2-layer shield with 1.5 cm gap in sinus MDCT,the radiation doses were reduced to 13.7 and 13.1 mGy with the reduction rates of 31.5％ and 34.5％ respectively.Conclusion The reasonable bismuth shielding can effectively reduce the radiation dose to eye lens in sinus CT on the premise of ensuring image-diagnostic quality.