Objective:To investigate the clinicopathological and genetic characteristics of malignant transformation of polyostotic fibrous dysplasia (FD) in long bone.Methods:A retrospective analysis of clinical characteristics and morphological features was conducted from 4 cases of malignant transformation of FD diagnosed at Beijing Jishuitan Hospital from January 2016 to December 2023. Hotspot mutations for GNAS gene were tested in 4 cases by Sanger sequencing, in which both FD and malignant tissues were detected in 3 cases respectively.Results:There were 2 female and 2 male patients, aged 46 to 53 years [mean (49±3.2) years], and the course of the disease spanned from 2 months to 36 years. The tumor involved the femur ( n=2), tibia ( n=1) and humerus ( n=1). Three of them were diagnosed with FD before surgery. Single photon emission computed tomography showed multiple increases in bone metabolism, CT showed poorly margin, cortical destruction and soft tissue mass with uneven enhancement. Three cases had both FD and sarcoma components, while the remaining case exhibited exclusively sarcoma. The sarcomas displayed significant morphological variation, with 1 case diagnosed as osteosarcoma and 3 cases classified as low to high grade spindle cell sarcoma. Immunohistochemical results did not provide any indications for clear classification. Sanger sequencing demonstrated GNAS mutations of p.R201H (c.CGT>CAT, n=2) and p.R201C (c.CGT>TGT, n=2). All 4 cases were followed-up for 18 to 76 months, and received chemotherapy after surgery; 2 cases maintained disease-free, one case was diagnosed with invasive breast cancer through a core needle biopsy 3 months after chemotherapy, and another one was found to relapse 18 months after surgery. Conclusions:Some cases of polyostotic FD occur in association with café-au-lait macules and/or endocrine hyperfunctioning in McCune-Albright syndrome (MAS); polyostotic FD and MAS have more malignant potential than monostotic FD, but they are not the risk factors for FD malignancy. GNAS mutations may be involved in the occurrence and development of FD. The histologic types of malignant transformation of polyostotic FD in long bone are diverse, the sarcoma components of FD also present the GNAS mutation, suggesting potential involvement in the pathogenesis of FD malignancy.

Objective:To investigate the clinicopathological and genetic characteristics of malignant transformation of polyostotic fibrous dysplasia (FD) in long bone.Methods:A retrospective analysis of clinical characteristics and morphological features was conducted from 4 cases of malignant transformation of FD diagnosed at Beijing Jishuitan Hospital from January 2016 to December 2023. Hotspot mutations for GNAS gene were tested in 4 cases by Sanger sequencing, in which both FD and malignant tissues were detected in 3 cases respectively.Results:There were 2 female and 2 male patients, aged 46 to 53 years [mean (49±3.2) years], and the course of the disease spanned from 2 months to 36 years. The tumor involved the femur ( n=2), tibia ( n=1) and humerus ( n=1). Three of them were diagnosed with FD before surgery. Single photon emission computed tomography showed multiple increases in bone metabolism, CT showed poorly margin, cortical destruction and soft tissue mass with uneven enhancement. Three cases had both FD and sarcoma components, while the remaining case exhibited exclusively sarcoma. The sarcomas displayed significant morphological variation, with 1 case diagnosed as osteosarcoma and 3 cases classified as low to high grade spindle cell sarcoma. Immunohistochemical results did not provide any indications for clear classification. Sanger sequencing demonstrated GNAS mutations of p.R201H (c.CGT>CAT, n=2) and p.R201C (c.CGT>TGT, n=2). All 4 cases were followed-up for 18 to 76 months, and received chemotherapy after surgery; 2 cases maintained disease-free, one case was diagnosed with invasive breast cancer through a core needle biopsy 3 months after chemotherapy, and another one was found to relapse 18 months after surgery. Conclusions:Some cases of polyostotic FD occur in association with café-au-lait macules and/or endocrine hyperfunctioning in McCune-Albright syndrome (MAS); polyostotic FD and MAS have more malignant potential than monostotic FD, but they are not the risk factors for FD malignancy. GNAS mutations may be involved in the occurrence and development of FD. The histologic types of malignant transformation of polyostotic FD in long bone are diverse, the sarcoma components of FD also present the GNAS mutation, suggesting potential involvement in the pathogenesis of FD malignancy.

Objective:To investigate the diagnostic value of detecting MDM2 gene amplification by fluorescence in situ hybridization (FISH) in low-grade osteosarcoma (LGOS).Methods:Thirty cases of parosteal osteosarcoma (POS) and 14 cases of low-grade central osteosarcoma (LGCOS) from April 2009 to August 2022 at Beijing Jishuitan Hospital, Capital Medical University were analyzed for the presence of MDM2 gene amplification by FISH. Fifty-eight additional cases were used as negative controls (including 28 cases of fibrous dysplasia, 5 cases of giant cell tumor, 4 cases of conventional osteosarcoma, 2 cases each of periosteal osteosarcoma, reparative changes after fracture, pleomorphic undifferentiated sarcoma, low grade myofibroblastic sarcoma, fibrous dysplasia with malignant transformation, one case each of leiomyosarcoma, sclerosing epithelioid fibrosarcoma, malignant peripheral nerve sheath tumor, desmoplastic fibroma of bone, solitary fibrous tumor, aneurysmal bone cyst, clear cell chondrosarcoma, osteofibrous dysplasia, and 3 cases of unclassified spindle cell tumor).Results:Among the 30 patients with POS, 15 were male and 15 were female, ranging in age from 10 to 59 years (mean 35 years, median 30.5 years). Among the 14 patients with LGCOS, four were male and 10 were female, ranging in age from 15 to 56 years (mean 37 years, median 36 years). All except one case were successfully detected by FISH. MDM2 gene amplification was detected in 27 cases of POS (27/29,91.3%) and 8 cases of LGCOS (8/14). All the negative controls were negative for MDM2 gene amplification. The positive rate of MDM2 gene amplification was significantly different between the case group and the control group ( P<0.05). The sensitivity and specificity of MDM2 gene amplification in diagnosing POS and LGCOS were 91.3% and 100.0%; and 57.1% and 100.0%, respectively. The sensitivity and specificity of MDM2 gene amplification in diagnosing LGOS (including POS and LGCOS) were 81.3% and 100.0%, respectively. In cases where MDM2 gene was amplified, the MDM2 amplified signal was clustered. Nine cases showed increased CEP12 signal different from polyploidy which was displayed as small and weak signal points or cloud flocculent and cluster signals. Conclusions:Detection of MDM2 gene amplification by FISH is a highly sensitive and specific marker for LGOS. The interpretation criteria for FISH detection of MDM2 amplification are currently not unified. The signal characteristics need more attention when interpreting.

Objective:To explore the mechanism underlying microRNA (miR) -125a-mediated inhibition of proliferation of keratinocytes.Methods:After 24-hour pretreatment with interleukin (IL) -23, human HaCaT keratinocytes were divided into miR-125a group and miR-NC group transfected with a miR-125a overexpression plasmid and a control plasmid, respectively. Cell counting kit-8 (CCK8) assay was performed to evaluate the proliferative ability of HaCaT cells in the two groups at 0, 24, 48 and 72 hours after transfection, real-time fluorescence-based quantitative PCR to determine the mRNA expression of miR-125a and IL-23 receptors (IL-23R) in the two groups 24 hours after transfection, and Western blot analysis to determine the protein expression of IL-23R, Janus kinase 2 (JAK2) , protein kinase B (AKT) and phosphorylated AKT (p-AKT) in the two groups 48 hours after transfection. Dual-luciferase reporter assay was performed to verify the targeting relationship between miR-125a and IL-23R. Comparison of means between two groups was carried out by using t test, and changes in the proliferative ability of HaCaT cells over time were evaluated by using repeated measures analysis of variance. Results:After plasmid transfection, the relative expression of miR-125a was significantly higher in the miR-125a group (6.377 ± 0.745) than in the miR-NC group (0.700 ± 0.222; t=7.305, P=0.002) . At 0, 24 and 48 hours after transfection, there was no significant difference in cellular proliferative ability between the miR-125a group and the miR-NC group ( t=0.663, 0.623 and 1.930, respectively, all P > 0.05) ; at 72 hours after transfection, the cellular proliferative ability was significantly lower in the miR-125a group than in the miR-NC group ( t=4.407, P < 0.05) . The IL-23R mRNA expression was significantly lower in the miR-125a group than in the miR-NC group ( t=3.082, P < 0.05) . Compared with the miR-NC group, the miR-125a group showed significantly decreased protein expression of IL-23R, JAK2 and p-AKT ( t=11.715, 6.996, 12.424, P < 0.001,=0.002, < 0.001, respectively) . Dual-luciferase reporter assay showed targeted binding of miR-125a to IL-23R. Conclusion:MiR-125a may inhibit the proliferation of keratinocytes by negatively regulating the IL-23R/JAK2/AKT signaling pathway.

Objective:To study the effect of culture supernatant of rat bone marrow mesenchymal stem cells (BMSCs) on biological characteristics of RSC96 Schwann cells.Methods: BMSCs of Sprague Dawley rat were cultured and purified in vitro.The BMSCs culture supernatant medium (BMSC-CM) was collected from the third generation of BMSCs.Using MTT method to detect proliferation influence of BMSC-CM on RSC96 cells,and using plate cloning assay to analysis a single cell proliferation effect.The migration analysis of BMSC-CM on RSC96 cells were detected by scratch and TranswellTM chamber assay,Western blot tested Bax and Bcl-2 proteins changes in RSC96 cells.Results: The third generation of BMSCs was long spindle-shaped and vortex-like;the result of Osteogenesis staining was positive;lipid droplets appeared after adipogenesis induction.BMSC-CM inhibited the proliferation and migration of RSC96 cells.Meanwhile,Bcl-2 protein decreased and Bax protein increased in RSC96 cells after BMSC-CM treatment.Conclusion: BMSC-CM can promote apoptosis and inhibit the proliferation and migration of RSC96 cells.

OBJECTIVE: To establish 2-dimensional gel electrophoresis (2-DE) image for the early lung injury rats induced by silica dioxide and to identify differentially expressed protein biomarkers during the early stage of silicosis.
 METHODS: The animal models of silicosis were established and morphology changes were observed by HE staining, and then the key protein biomarkers in silicosis were identified by 2-DE and matrix-assisted laser desorption/ionization time of flight tandem mass spectrometry (MALDI-TOF-MS) and verified by Western blot.
 RESULTS: The well qualified 2-DE gel images for experimental and control lung tissues were successfully established, and 40 different protein spots was observed when comparing the gel images between the experimental and control groups. Twenty of them were analyzed by MALDI-TOF-MS. A total of 13 altered proteins were identified, including alpha B-crystallin, mast cell protease 6, annexin 1, etc. The expression of alpha B-crystallin in lung was further verified by Western blot.
 CONCLUSION The protein expression of alpha B-crystallin was increased significantly, suggesting that it might play an important role in the progress of silicosis.
Animals ; Biomarkers ; metabolism ; Blotting, Western ; Disease Models, Animal ; Electrophoresis, Gel, Two-Dimensional ; Lung ; metabolism ; pathology ; Proteomics ; Rats ; Silicon Dioxide ; adverse effects ; Silicosis ; diagnosis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; alpha-Crystallin B Chain ; metabolism

BACKGROUNDThe performance of computed tomography X-ray absorptiometry (CTXA) against the dual energy X-ray absorptiometry (DXA) as standard has not been studied in Chinese population. The aim of this study was to evaluate the precision of this measurement and validate the value of quantitative computed tomography (QCT) by comparing CTXA results with DXA results in an elderly Chinese population.

METHODSOne hundred and three females of 46 to 76 years old and 49 males of 52 to 76 years old were recruited from the Prospective Urban Rural Epidemiology study. All subjects underwent hip scans by both QCT and DXA on the same day. For precision determination, 30 subjects had duplicate DXA hip scans. The hip QCT data of a subset of 27 subjects were separately analyzed by two observers and reanalyzed by one observer at a different time. The inter- and intra-observer variations of CTXA measurement were assessed, and the difference and correlation between CTXA and DXA results were analyzed.

RESULTSThe inter- and intra-observer variations of CTXA were 0.070 and 0.024 g/cm(2) in the femoral neck (FN), and 0.030 and 0.012 g/cm(2) in the total hip (TH), which were comparable to the DXA inter-scan variations (0.013 g/cm(2) for FN and 0.014 g/cm(2) for TH). The results of CTXA bone mineral density (BMD) were highly correlated with those of DXA (R(2) = 0.810 for FN and R(2) = 0.878 for TH). The BMD values of CTXA in FN and TH were lower than those of DXA by 21.0% and 17.8% (P < 0.05), respectively. However, after appropriate transformation, the difference was eliminated and a comparable T score could be obtained.

CONCLUSIONSCTXA shows good agreement with DXA for the measurement of BMD in the proximal femur, which makes QCT suitable for the quantification of bone mineral content in the hip and helpful for the diagnosis of osteoporosis.

Absorptiometry, Photon ; methods ; Aged ; Bone Density ; physiology ; Female ; Humans ; Male ; Middle Aged ; Osteoporosis ; diagnosis ; diagnostic imaging ; Tomography, X-Ray Computed

OBJECTIVETo investigate the association of single nucleotide polymorphisms in the HLA-DP and DQ genes with the outcome of chronic hepatitis B virus infection.

METHODSTwo hundred and four healthy subjects, 255 clearance subjects, 204 asymptomatic HBV carriers (AsC), 136 chronic hepatitis B (CHB), 68 liver cirrhosis (LC) and hepatocellular carcinoma (HCC) were enrolled. Genotypes of rs3077, rs9277535 and rs2647050 were determined by sequence specific primers-PCR (PCR-SSP).

RESULTSBy using healthy subjects and clearance subjects as the control groups, rs3077 and rs9277535 were significantly associated with chronic HBV infection under additive and dominant models (P< 0.05). Meanwhile, haplotypes GGA, AGA, AAA appeared to be protective factors against chronic HBV infection (P < 0.05). By using AsC as the control group, comparison with the CHB, LC and HCC groups showed no association of the 3 SNPs or haplotypes with the clinical outcome (P > 0.05).

CONCLUSIONHLA-DP gene polymorphisms are strongly associated with chronic HBV infection. The presence of A allele at rs3077 and rs9277535 of the HLA-DP gene may decreased the risk for chronic HBV infection.

Adult ; Asian Continental Ancestry Group ; ethnology ; genetics ; Case-Control Studies ; China ; ethnology ; Female ; Genotype ; HLA-DP Antigens ; genetics ; HLA-DQ Antigens ; genetics ; Hepatitis B virus ; physiology ; Hepatitis B, Chronic ; ethnology ; genetics ; virology ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

Objective To analyze the clinical and imaging features of pulmonary metastasis of giant cell tumor of bone for clinical diagnosis and treatment.Methods Five patients with histologically proven pulmonary metastasis from giant cell tumor of bone were reviewed,the imaging features and the progression of the pulmonary metastasis were evaluated.Results The first operation of primary tumor was curettages and then local recurrence was seen in all 5 cases.The interval to metastasis ranged from 5 to 26 months.Pulmonary metastasis was diagnosed by chest radiographs in 4 cases and CT in all 5 cases.The imaging findings included solitary solid nodule (n =1),multiple solid nodules and mass (n =5),multiple groundglass nodules (n =1) and complex form (n =2).The dynamic follow-up CT findings showed spontaneous regress nodules (n =1),metastasis occurring again 19 months after surgery of solitary nodule (n =1),some solid nodules unchangable for a long time in 3 patients with multiple nodules.Conclusions The dynamic follow-up CT findings of pulmonary metastasis of giant cell tumor of bone are specific.The regular follow-up could play an essential role in early detection and prognosis of pulmonary metastasis within 2 years after primary tumor diagnosed.

Objective To evaluate the feasibility of assessing osteoarthritis (OA) in hip dysplasia using 3D delayed gadolinium-enhanced MRI of cartilage (dGEMRIC).Methods Thirty-five hips in 20 patients with radiographic evidence of hip dysplasia underwent 3D-dGEMRIC scanning.Clinical symptoms were assessed with the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) questionnaire.Radiographic measurement of lateral center-edge angle and T(o)nnis grading were performed on the X-rays.Hips of T(o)nnis grade 1were included in the group of hips with early OA,while the hips with no evidence of OA and without pain symptom were included in the group of hips with normal morphology.The 3D-dGEMRC scans were completed on a 1.5 T MR scanner.The data of 3D-dGEMRIC was reconstructed radically.The dGEMRIC indices were measured on six sites of periphery zones of hip cartilage on reconstructed images.The dGEMRIC indices among different groups were analyzed by non-parametric tests.The differences of dGEMRIC indices among six sites in the group of early OA or the group of normal morphology were analyzed by Wilcoxon test.Results The mean dGEMRIC indices of six sites were lower in group of T(o)nnis grade 1than in group of T(o)nnis grade 0 ( Z =- 2.149,P =0.032 ),and lower in group of T(o)nnis grade 2 than in group of T(o)nnis grade 1( Z =- 1.990,P =0.047 ).The dGEMRIC indices of the anterior site,anterosuperior site,superior-anterior site,and superior site were significantly different between the group of hips with early OA and the group of hips with normal morphology (Z =-2.333--2.041,all of the P values were lower than 0.05).In the group of hips with normal morphology,the dGEMRIC indices of superior-anterior site of hip were lower than superior site(P =0.028).In the group of hips with early OA,the dGEMRIC indices of superior-anterior site were lower than the other sites except for anterior-superior site ( Z =- 3.041- - 2.277,all of the P values were lower than 0.05 ).Conclusions 3 D-dGEMRIC might be a sensitive technique for detection of glycosaminoglycans alteration in early OA and staging of OA in hip dysplasia.Radial reconstruction could provide an accurate assessment of OA,and the results demonstrated that early cartilage alteration could be detected in the anterior to superior sites of hips,and the earliest cartilage alteration may occur in the superior-anterior site of hips.