Objective To investigate the expressions of H3.3G34W,p63 and SATB2 in giant cell tumor of bone(GCTB)and the effect and value of their combined application in the diagnosis of GCTB.Methods We collected the samples and medical records of 54 cases of GCTB and 83 cases of non-giant cell tumor of bone(14 cases of aneurysmal bone cyst,16 cases of chondroblastoma and 53 cases of non-ossifying fibroma)diagnosed between 2020 and 2022 in the Department of Pathology of Honghui Hospital Affiliated to Xi'an Jiaotong University.The expressions of H3.3G34W,p63 and SATB2 were detected by EliVision immunohistochemical method.X2 test was used to determine whether there are significant differences in the positive rates of H3.3G34W,p63 and SATB2 among all the groups.The combined diagnostic model including H3.3G34W,p63 and SATB2 was established by Logistic regression analysis,and the diagnostic value of the model was evaluated by ROC curve analysis.Results The positive rates of H3.3G34W,p63 and SATB2 in GCTB group were 81.5％,90.7％and 92.6％,respectively;the positive rates in NGCTB group were 2.4％,28.9％and 62.7％.Compared with NGCTB group,the age of GCTB group was significantly older[(41.222±14.849)vs.(16.566±9.439),P＜0.001],and the prevalence was higher in women than in men(51.9％vs.48.1％,P＜0.001).In addition,compared with the NGCTB group,the positive rates of H3.3G34W(81.5％vs.2.4％,P＜0.001),p63(90.7％vs.28.9％,P＜0.001)and SATB2(92.6％vs.62.7％,P＜0.001)were significantly higher in the GCTB group.Univariate regression analysis built a univariate prediction modeland ROC curve analysis showed that age(AUC=92.9％,P＜0.001),sex(AUC=64.5％,P=0.004),H3.3G34W positive rate(AUC=89.5％,P＜0.001),p63 positive rate(AUC=80.9％,P＜0.001)and SATB2 positive rate(AUC=65.0％,P=0.003)were independent predictors of diagnosis of giant cell tumor of bone.Multivariate regression analysis(Logistic)constructed a hybrid prediction model.ROC curve analysis suggested that the hybrid model showed better prediction value than the single factor model(AUC=98.4％,P＜0.001).Conclusion H3.3G34W,p63 and SATB2 are effective molecular markers for the diagnosis of GCTB,and their combined application can improve the prediction efficiency of the diagnosis of GCTB.

Objective To observe the effectiveness and safety of Neuron MAX sheath applicated in transradial access(TRA)neurointervention.Methods Data of 44 patients with cerebrovascular disease who underwent TRA neurointervention using Neuron MAX sheath were retrospectively analyzed.The operative success rate,the adverse events during and after operation were recorded,and the occlusion of radial artery 6 months after treatment were followed up.Results The operative success rate of TRA neurointervention using Neuron MAX sheath was 95.45%(42/44).Neuron MAX sheath kinked during operation in 2 cases,but intervention treatment were successfully performed through transfemoral access.After treatments,aneurysms in 27 cases were successfully embolized,and symptomatic intracranial atherosclerotic stenosis in 14 cases were successfully treated with simple balloon dilation(2 cases)or/and stenting(12 cases),whereas carotid-cavernous fistulas completely disappeared in 2 cases,and cerebral arteriovenous malformation achieved curative embolization in 1 case.Asymptomatic dissection of brachiocephalic trunk occurred in 1 case during intervention,and CT showed infarction in right temporoparietal lobe in 1 patient who underwent embolization of right middle cerebral artery aneurysm.Radial artery occlusion was found in 6 patients 6 months after treatments.Conclusion Neuron MAX sheath was effective and safe for TRA neurointervention.

OBJECTIVE: To summarize the gene therapy strategies for neurofibromatosis type 1 (NF1) and related research progress. METHODS: The recent literature on gene therapy for NF1 at home and abroad was reviewed. The structure and function of the NF1 gene and its mutations were analyzed, and the current status as well as future prospects of the transgenic therapy and gene editing strategies were summarized. RESULTS: NF1 is an autosomal dominantly inherited tumor predisposition syndrome caused by mutations in the NF1 tumor suppressor gene, which impair the function of the neurofibromin and lead to the disease. It has complex clinical manifestations and is not yet curable. Gene therapy strategies for NF1 are still in the research and development stage. Existing studies on the transgenic therapy for NF1 have mainly focused on the construction and expression of the GTPase-activating protein-related domain in cells that lack of functional neurofibromin, confirming the feasibility of the transgenic therapy for NF1. Future research may focus on split adeno-associated virus (AAV) gene delivery, oversized AAV gene delivery, and the development of new vectors for targeted delivery of full-length NF1 cDNA. In addition, the gene editing tools of the new generation have great potential to treat monogenic genetic diseases such as NF1, but need to be further validated in terms of efficiency and safety. CONCLUSION Gene therapy, including both the transgenic therapy and gene editing, is expected to become an important new therapeutic approach for NF1 patients.
Humans ; Neurofibromatosis 1/pathology* ; Neurofibromin 1/metabolism* ; GTPase-Activating Proteins ; Mutation ; Genetic Predisposition to Disease ; Genetic Therapy

Humans ; Neoplasms, Second Primary/epidemiology* ; Neoplasms/epidemiology* ; Risk Factors ; Prognosis

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca²⁺ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca²⁺-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

Neurofibromatosis type Ⅰ(NF1)is an autosomal dominant genetic disease triggered by mutations of nf1gene, nf1 gene and its encoded protein product neurofibromatoprotein play important roles in tumor supressive activity. Plexiform neurofibroma was the main manifestation among some patients For plexiform neurofibroma, surgical treatment did not have satisfactory effect. meanwhile, traditional radiotherapy and chemotherapy are ineffective. All of those above serve as challenges for clinical treatment and have been received much more attention from study of multimoics and targeting therapy In this Review, the clinical features of NF1-associated plexiform neurofibromasand, the progress regarding investigation of drug targets and clinical trials for the drug of plexiform neurofibroma will be presented.

Objective:To explore the relationship of telomere length, mitochondrial DNA copy number of peripheral blood with hypertension and the interaction between telomere length and mtDNA-CN on hypertension in coal miners.Methods:A case control study was conducted in a coal mine of Shanxi province from July to December of 2013, in which 325 healthy workers were selected as the control group and 378 workers with hypertension as the case group. The information about general demographic characteristics and life behavior habits of the subjects were collected through questionnaire. Levels of telomere length and mtDNA-CN in peripheral blood were detected by real-time PCR. Unconditional logistic regression was used to examine the association between hypertension and telomere length, mtDNA-CN. The interaction test between telomere length and mtDNA-CN on hypertension was performed by adding the interaction term in the corresponding model.Results:The mean telomere length of the workers in the case group was (1.50±0.55) kb, and that of the control group was (2.01±0.62) kb, the difference between two groups was significant ( t=11.68, P<0.001). The correlation analysis showed that telomere length was positively correlated with mtDNA-CN ( r=0.157, P=0.002) in the case group. Multivariate analysis showed that telomere length ( OR=4.408, 95% CI: 3.012-6.452), age ( OR=0.417, 95% CI: 0.284-0.613), BMI ( OR=1.357, 95% CI: 1.162-1.584), monthly household income level ( OR=0.656, 95% CI: 0.553-0.778) and work duration ( OR=1.249, 95% CI: 1.100-1.417) were influencing factors of hypertension. The multiply interaction between telomere length and mtDNA-CN was significant on hypertension ( OR=1.267, 95% CI: 1.094-1.468). Conclusions:The results suggest shorter telomere length is a risk factor of hypertension. There is a multiply interaction between telomere length and mtDNA-CN on hypertension. However, the association between mtDNA-CN and hypertension was not found.

Objective:To investigate the value of serum urea nitrogen on in-hospital death in patients with heart failure.Methods:The clinical data of 9 459 patients with heart failure from January 2013 to December 2018 in Shengjing Hospital of China Medical University were retrospectively analyzed. Among them, 296 cases died in hospital (death group) and 9 163 cases survived (survival group). The clinical data of patients were collected, including general condition, disease history, physical examination, laboratory indicators and relevant physical examination, etc. Correlation was finished with Pearson correlation analysis. Multivariate Logistic regression analysis was used to determine independent risk factors for in-hospital death in patients with heart failure. Receiver operating characteristic (ROC) curve was used to determine the optimal predictive threshold of urea nitrogen for in-hospital death.Results:The in-hospital mortality in patients with heart failure was 3.1% (296/9 459). There were statistical differences in age, hypertension rate, diabetes rate, a history of atrial fibrillation rate, smoking history rate, hemoglobin, albumin, glycosylated hemoglobin, urea nitrogen, creatinine, uric acid, serum potassium, serum sodium, troponin I, N terminal brain natriuretic peptide precursor (NT-proBNP), left ventricular ejection fraction (LVEF) between death group and survival group ( P<0.01 or <0.05), and there were no statistical difference in gender composition, coronary heart disease rate, platelet, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride, left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) between 2 groups ( P>0.05). Pearson correlation analysis result showed that the urea nitrogen was positively correlated with age, coronary heart disease, hypertension, diabetes, glycosylated hemoglobin, creatinine, uric acid, serum potassium, troponin I, NT-proBNP, LVEDV and LVESV ( r = 0.130, 0.024, 0.053, 0.128, 0.033, 0.739, 0.468, 0.377, 0.065, 0.432, 0.084 and 0.101; P<0.01 or <0.05); and the urea nitrogen was negatively correlated with gender, history of atrial fibrillation, hemoglobin, platelet, albumin, total cholesterol, LDL-C, serum sodium and LVEF ( r = -0.033, -0.063, -0.272, -0.077, -0.188, -0.070, -0.071, -0.199 and -0.113, P<0.01); and there were no correlation between urea nitrogen and smoking history or triglyceride ( P>0.05). Multivariate Logistic regression analysis result showed that age, hypertension, albumin, urea nitrogen, troponin I and NT-proBNP were independent risk factors for in-hospital death in patients with heart failure ( OR = 1.018, 0.613, 0.924, 1.082, 1.340 and 1.005; 95% CI 1.002 to 1.033, 0.427 to 0.881, 0.889 to 0.961, 1.040 to 1.126, 1.111 to 1.617 and 1.003 to 1.007; P<0.05 or <0.01). ROC curve analysis result showed that the area under the curve (AUC) of urea nitrogen for prediction of in-hospital death in patients with heart failure was 0.737 (95% CI 0.728 to 0.748), and the optimal threshold value was 11.41 mmol/L, with a sensitivity of 60.16% and a specificity of 77.01%; the AUC of NT-proBNP for prediction of in-hospital death in patients with heart failure was 0.726 (95% CI 0.712 to 0.740), and there was no statistical difference in the AUC between urea nitrogen and NT-proBNP ( Z=1.055, P=0.291). Conclusions:Elevated urea nitrogen level is independently associated with an increase in in-hospital mortality in patients with heart failure, and the optimal threshold for predicting in-hospital death is 11.41 mmol/L.

BACKGROUND:Currently, bioactive glass and polylactic acid have been used in clinical dentistry and plastic surgery; however, their therapeutic outcomes are not satisfactory, because the material properties have some limitations. OBJECTIVE:To explore the cytocompatibility of oxygen plasma-treated polylactic acid and bioactive glass guided bone regeneration membrane. METHODS:Bioactive glass and polylactic acid were used as the basic materials to prepare polylactic acid membrane, polylactic acid and bioactive glass composite membrane and oxygen plasme-treated polylactic acid and bioactive glass composite membrane, al of which were used to culture MG63 cels. Cel adhesion rate, cel proliferation rate and alkaline phosphatase activity of MG63 cels on these three kinds of membranes were observed. RESULTS AND CONCLUSION: With the growth of time, in these three groups of membranes, the cel adhesion rate and cel proliferation rate were al significantly increased. Alkaline phosphatase activity showed a decreasing trend after the first increase, and reached its peak at the 7thday of culture. The cel adhesion rate and cel proliferation rate in oxygen plasma-treated polylactic acid and bioactive glass group were significantly higher than those in the other two groups, while the cel adhesion and proliferation rates in polylactic acid and polylactic acid and bioactive glass groups were similar. At the 3rd day of culture, the alkaline phosphatase activity in the polylactic acid and bioactive glass group and oxygen plasma-treated polylactic acid and bioactive glass group was significantly higher than that in the polylactic acid group. At the 7th and 14th days, there was no significant difference in the alkaline phosphatase activity among these three groups. These results show that oxygen plasma-treated polylactic acid and bioactive glass composite membrane has good biocompatibility, which can better promote cel adhesion, proliferation and matrix secretion from osteogenic cels.

Objective To determine the effect of primary realignment of posterior urethral injury associated with pelvic fracture on length and delayed operative treatment of ensuing urethral stricture.Methods A retrospective review was made on the clinical data of 64 patients with posterior urethral injury after pelvic fracture treated from January 2008 to January 2012.Of those patients,43 underwent primary endoscopic realignment (early realignment group) and 30 received primary suprapubic cystostomy (cystostomy group).All were evaluated postoperatively for the late stricture rate,stricture length,types of delayed repair,and operation frequency.Results Rate of stricture was 53％ (18/34) in early realignment group and 100％ (30/30) in cystostomy group,but all were corrected by delayed urethroplasty.Mean length of the stricture was (1.8±0.6) cm in early realignment group and (2.9±0.7)cm in cystostomy group(t=6.7,P＜0.05).Of the urethrostenosis patients in early realignment group,83％ (15/18) were successfully corrected with a simple endoscopic cold incision and 17％ (3/18) with open surgery.In contrast,only 60％ (18/30) in cystostomy group were successfully corrected by endoscopic cold incision.Patients in cystostomy group underwent (2.8 ± 0.5) procedures for cure compared with (1.6 ± 0.6) procedures in early realignment group (t =9.2,P＜0.05).Conclusion Primary endoscopic realignment for posterior urethral injury pelvic fracture offers the decrease in stricture incidence,stricture length,operation difficulty and operation frequency.