Objective:To investigate the influencing factors for lymph node metastasis and prognosis in stage T1 and T2 esophageal squamous cell carcinoma after radical surgery and construct nomogram prediction models.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 672 patients with T1 and T2 esophageal squamous cell carcinoma who were admitted to the Affiliated Hospital of North Sichuan Medical College from January 2014 to December 2019 were collected. There were 464 males and 208 females, aged (65±8)years. All patients under-went radical esophagectomy+2 or 3 field lymph node dissection. Observation indicators: (1) lymph node dissection, metastasis and follow-up. (2) risk factors for lymph node metastasis of esophageal cancer after radical resection. (3) prognostic factors of esophageal cancer after radical resection. (4) construction and evaluation of the prediction models of lymph node metastasis and prognosis of esophageal cancer after radical resection. Follow-up was conducted using outpatient examination, telephone and internet consultations to detect survival of patients up to April 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Kaplan-Meier method was used to calculate survival rate and draw survival curve. Log-Rank test was used for survival analysis. Logistic regression model was used for univariate and multivariate analyses of risk for lymph node metastasis, and COX regression model was used for univariate and multivariate analyses of prognosis. Based on the results of multi-variate analysis, the nomogram prediction models for lymph node metastasis and prognosis predic-tion were constructed. The prediction discrimination of the nomogram models were evaluated using the area under curve (AUC) of the receiver operating characteristic curve (ROC). The calibration curve was used to evaluate the prediction consistency of the models. Results:(1) Lymph node dissection, metastasis and follow-up. The number of lymph node dissected was 14±8 and the number of lymph node metastasis was 2(range, 1?19) in 672 patients. Of the 672 patients, there were 182 cases had lymph node metastasis, including 58 cases in T1 stage and 124 cases in T2 stage. All 672 patients were followed up for 38 (range, 1?85)months. The average overall survival time of 672 patients was 65 months, with the 1-, 3-, 5-year overall survival rate as 89.0%, 74.3%, 66.0%, respectively. The average overall survival time of 325 patients in T1 stage and 347 patients in T2 stage were 70 months and 61 months. The 1-, 3-, 5-year overall survival rate of 325 patients in T1 stage and 347 patients in T2 stage were 95.0%, 83.5%, 73.4% and 87.4%, 69.9%, 59.2%, respectively, showing a significant difference in survival between them ( χ2=14.51, P<0.05). (2) Risk factors for lymph node metastasis of esophageal cancer after radical resection. Results of univariate analysis showed that tumor location, tumor histological grade, tumor T staging were related factors affecting lymph node metastasis of esophageal cancer after radical resection ( odds ratio=1.40, 1.54, 2.56, 95% confidence interval as 1.07?1.85, 1.20?1.99, 1.79-3.67, P<0.05). Results of multivariate analysis showed that tumor location, tumor histological grade, tumor T staging were independent factors affecting lymph node metastasis ( odds ratio=1.42, 1.61, 2.63, 95% confidence interval as 1.07?1.89, 1.25?2.09, 1.82?3.78, P<0.05). (3) Prognostic factors of esophageal cancer after radical resection. Results of univariate analysis showed that preoperative comorbidities, postoperative complications, tumor histological grade (G3), tumor T staging, tumor N staging (N1 stage, N2 stage, N3 stage), tumor TNM staging (Ⅲ stage, Ⅳ stage) were related factors affecting prognosis of esophageal cancer after radical resection ( hazard ratio= 1.48, 1.64, 2.23, 1.85, 2.09, 4.48, 4.97, 3.54, 5.53, 95% confidence interval as 1.08?2.03, 1.20?2.23, 1.47?3.39, 1.34?2.54, 1.44?3.04, 2.89?6.95, 1.57?15.73, 2.48?5.05, 1.73?17.68, P<0.05). Results of multivariate analysis showed that preoperative comorbidities, G3 of tumor histological grade, T2 stage of tumor T staging, N1 stage, N2 stage, N3 stage of tumor N staging were independent risk factors affecting prognosis of esophageal cancer after radical resection ( hazard ratio=1.57, 1.89, 1.63, 1.71, 3.72, 3.90, 95% confidence interval as 1.14?2.16, 1.23?2.91, 1.17?2.26, 1.16?2.51, 2.37?5.83, 1.22?12.45, P<0.05). (4) Construction and evaluation of the prediction models of lymph node metastasis and prognosis of esophageal cancer after radical resection. Based on the results of multivariate analysis, tumor location, tumor histological grade, tumor T staging were applied to construct a nomo-gram model for lymph node metastasis prediction of esophageal cancer after radical resection, the score of tumor location, tumor histological grade, tumor T staging were 82, 100, 100, respectively, and the sum of the scores corresponding to the lymph node metastasis rate. Preoperative comor-bidity, tumor histological grade, tumor T staging, tumor N staging were applied to construct a nomo-gram model for 1-, 3-, 5-year overall survival rate prediction of esophageal cancer after radical resection, the score of preoperative comorbidity, tumor histological grade, tumor T staging, tumor N staging were 23, 38, 27, 100, respectively, and the sum of the scores corres-ponding to the 1-, 3-, 5-year overall survival rate. Results of ROC showed that the AUC of nomogram model for lymph node metastasis prediction after radical esophagectomy was 0.66 (95% confidence interval as 0.62?0.71, P<0.05). The AUC of nomogram model for 1-, 3-, 5-year overall survival rate prediction after radical esophagectomy were 0.73, 0.74, 0.71 (95% confidence intervals as 0.66?0.80, 0.68?0.79, 0.65?0.78, P<0.05). Results of calibration curve showed that the predicted lymph node metastasis rate and the predicted 1-, 3-, 5-year overall survival rate by nomogram models were consistent with the actual lymph node metastasis rate and 1-, 3-, 5-year overall survival rate. Conclusions:Tumor location, tumor histological grade, tumor T staging are independent factors affecting lymph node metastasis in T1 and T2 esophageal squamous cell carcinoma after radical surgery and nomogram model constructed by these indicators can predict the lymph node metas-tasis rate. Preoperative comor-bidities, G3 of tumor histological grade, T2 stage of tumor T staging, N1 stage, N2 stage, N3 stage of tumor N staging are independent risk factors affecting prognosis and nomogram model constructed by these indicators can predict the overall survival rate of patients after surgery.

Objective:To evaluate the prognostic significance of clonal gene mutations using next-generation sequencing in patients with core-binding factor acute myeloid leukemia (CBF-AML) who achieved first complete remission after induction chemotherapy.Methods:The study, which was conducted from July 2011 to August 2017 in First Affiliated Hospital of Soochow University, comprised 195 newly diagnosed patients with CBF-AML, including 190 patients who achieved first complete remission after induction chemotherapy. The cohort included 134 patients with RUNX1-RUNXIT1 + AML and 56 patients with CBFβ-MYH11 + AML. The cohort age ranged from 15 to 64 years, with a median follow-up of 43.6 months. Overall survival (OS) and disease-free survival (DFS) were assessed by the log-rank test, and the Cox proportional hazards regression model was used to determine the effects of clinical factors and genetic mutations on prognosis. Results:The most common genetic mutations were in KIT (47.6% ) , followed by NRAS (20.0% ) , FLT3 (18.4% ) , ASXL2 (14.3% ) , KRAS (10.7% ) , and ASXL1 (9.7% ) . The most common mutations involved genes affecting tyrosine kinase signaling (76.4% ) , followed by chromatin modifiers (29.7% ) . Among the patients receiving intensive consolidation therapy, the OS tended to be better in patients with CBFβ-MYH11 + AML than in those with RUNX1-RUNXIT1 + AML ( P=0.062) . Gene mutations related to chromatin modification, which were detected only in patients with RUNX1-RUNXIT1 + AML, did not affect DFS ( P=0.557) . The patients with mutations in genes regulating chromatin conformation who received allo-hematopoietic stem cell transplantation (allo-HSCT) achieved the best prognosis. Multivariate analysis identified KIT exon 17 mutations as an independent predictor of inferior DFS in patients with RUNX1-RUNXIT1 + AML ( P<0.001) , and allo-HSCT significantly prolonged DFS in these patients ( P=0.010) . Conclusions:KIT exon 17 mutations might indicate poor prognosis in patients with RUNX1-RUNXIT1 + AML. Allo-HSCT may improve prognosis in these patients, whereas allo-HSCT might also improve prognosis in patients with mutations in genes related to chromatin modifications.

OBJECTIVE: To carry out genetic testing for a pedigree affected with carotid body tumor (CBT). METHODS: Members of the pedigree were enrolled and underwent physical examination, ultrasonography and CT scan. Genomic DNA of the proband was extracted from peripheral blood sample and subjected to exome sequencing. Candidate variants were predicted using bioinformatic tools and verified among members from his pedigree. RESULTS: A c.170-1G>T splicing variant of the SDHD gene was detected in 15 individuals from the pedigree. Physical examination and imaging confirmed that 9 of them had CBT and hypertension, while the remaining 6 died of cardiovascular and cerebrovascular diseases. CONCLUSION The c.170-1G>T variant of the SDHD gene probably underlies the CBT in this pedigree. Genetic testing should be considered for CBT patients with CBT in addition to conventional clinical examination.

Objective To investigate the expression of miRNA-140 in chondrocytes and synovial fluid of osteoarthritis (OA) patients, and explore the relationship between the miRNA-140 expression and OA severity.Methods This study enrolled 30 OA patients who underwent total knee arthroplasty for chondrocytes sampling and 30 OA patients who underwent intra-articular injection for synovial fluid sampling. All OA patients were grouped into mild [Kellgren and Lawrence (KL) grade 1-2], moderate (KL grade 3) and severe (KL grade 4), with 10 in each subgroups for each sampling purposes. 7 non-OA patients and 10 patients with knee injury were collected for cartilage and synovial fluid sampling respectively as control groups. Chondrocytes were isolated from the cartilage tissue and cultured in vitro. Quantitative real time PCR for miRNA-140 in chondrocytes and synovial fluid were performed, and the U6 snRNA was used as internal control. The expression difference of miRNA-140 among groups and correlation between the expression and the KL grade of OA were analysed using one-way ANOVA and Spearman test respectively. Results The expression of miRNA-140 in chondrocytes of knees in OA patients was reduced than that in normal knees, and the between-group difference was statistically significant (F=305.464, P<0.001). miRNA-140 could be detected in synovial fluid of both normal knees and OA knees, its relative expression level was reduced in synovial fluid of OA group compared with normal group, and the between-group difference was statistically significant as well (F=314.245, P<0.001). The relative expression level of miRNA-140 in both chondrocytes and synovial fluid were negatively correlated with the KL grade of OA(r=-0.969, P<0.001; r=-0.970, P<0.001). Conclusion miRNA-140 could be detected in chondrocytes and synovial fluid of OA patients, and its expression was negatively correlated with the severity of OA.
Adult ; Aged ; Cells, Cultured ; Chondrocytes ; metabolism ; Female ; Humans ; Knee Joint ; metabolism ; Male ; MicroRNAs ; analysis ; Middle Aged ; Osteoarthritis, Knee ; metabolism ; Real-Time Polymerase Chain Reaction ; Synovial Fluid ; metabolism

This study was aimed to create strontium-calcium sulfate compounds for making a new bioactive material with osteoconductive and osteoinduceable activity for bone repairing. Its mechanics and degradation features were assessed in vitro. Powders of alpha-calcium sulfate hemihydrate (alpha-CSH) and SrCl2 were mixed completely to make Sr-calcium sulfate compounds materials with 6 different concentrations (0%, 0.1%, 0.3%, 0.5%, 1% and 2%) of Sr. Scanning electron microscope was used to observe the configuration of the new materials. The compressive strength of each material was tested. The materials were soaked into simulated body fluid (SBF) to test the features of degradation, which included pH, weight loss, declination of compressive strength and the changes of strontium ion concentration. The crystal appearances were influenced by incorporating of strontium. The compressive strength of non-strontium incorporating calcium sulfate was 36.65 +/- 2.22 MPa. When the concentration of strontium was increasing, the compressive strength measurements of the materials tended to decline. The compressive strength declined to 20.56 +/- 2.64 MPa when the strontium concentration reached to 2%. The pH value of the SBF declined when the time of degradation increased, but both of them were very stable. All of the materials got weight loss after being soaked in SBF for several weeks. The weight loss was slight within 4 weeks and it became dramatic after 4 weeks. When the concentration of strontium was increasing, the weight loss became more rapid and significant (P<0.05). During 0-4 weeks' degradation in SBF, the materials' compressive strength decreased much slower when the strontium concentration was below 0.5%; however, when the decrement of strength became faster, the strontium concentration became higher. The concentration of strontium ion in SBF began to increase faster after 4 weeks' soaking in SBF. As the concentration of strontium was increasing, the strontium ion concentration in SBF became higher (P = 0.000). The new compound materials made by the mixing of alpha-calcium sulfate hemihydrate and SrCl2 can provide efficient compressive strength. The features of degradation of the materials are very stable. The new materials can release lots of bone inducible substance-strontium ions to repair bone defection after 4 weeks of degradation.
Bone Substitutes ; chemical synthesis ; chemistry ; Calcium Sulfate ; chemistry ; Compressive Strength ; Humans ; Osteogenesis ; Strontium ; chemistry