Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Objective:To analyze the prognosis and influencing factors of different radiotherapy modes in patients with brain metastases from non-small cell lung cancer (NSCLC), and to explore the best benefit population with radiotherapy boost under different prognostic scores.Methods:634 patients with brain metastasis from NSCLC admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different radiotherapy modes, they were divided into three groups: no radiotherapy group ( n=330), whole-brain radiotherapy group (WBRT)( n=127) and whole-brain radiotherapy combined with boost group (WBRT+ boost)( n=177). The intracranial progression-free survival (iPFS) and overall survival (OS) were calculated by Kaplan-Meier method. The multivariate prognostic factors were analyzed by the Cox models. Results:The median iPFS and OS of all patients were 6.9 months and 9.0 months, respectively. In the no radiotherapy, WBRT and WBRT+ boost groups, the 1-year iPFS was 15.1%, 16.3% and 40.2%( P=0.002), and the 1-year OS was 33.7%, 38.2% and 48.1%( P<0.001), respectively. Multivariate survival analysis demonstrated that different radiotherapy modes were the independent factors affecting iPFS and OS. Subgroup analysis revealed that for patients with 1-3 brain metastases, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone ( P=0.026, P=0.044) when GPA score was 2.5-4.0; the 1-year OS and iPFSin the WBRT+ boost group were better than those of WBRT alone ( P=0.036, P=0.049) when there was no targeted therapy; for patients with ≥4 brain metastases, the 1-year iPFS in the WBRT+ boost group was better than that of WBRT alone ( P=0.019, P=0.012) when GPA score was 2.5-4.0 and there was no targeted therapy. When the GPA score was 0-2 or there was targeted therapy, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone, but the difference was not statistically significant (all P>0.05). Conclusions:Radiotherapy can significantly improve the iPFS and OS of NSCLC patients with brain metastases. When the number of brain metastases is 1-3, GPA score is 2.5-4.0 or no targeted therapy, boost may improve the iPFS and OS; when the number of brain metastases is more than 4, GPA score is 2.5-4.0 or no targeted therapy, boost may only bring iPFS benefit; when GPA score is 0-2 or targeted therapy, boost may not benefit significantly.

Objective:To analyze the prognosis and influencing factors of patients with brain metastases from non-small cell lung cancer (NSCLC) treated with different doses of whole brain radiotherapy (WBRT).Methods:A total of 244 NSCLC patients with brain metastases who underwent WBRT in the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different doses of WBRT (EQD 2Gy), they were divided into the 30-39 Gy group ( n= 104) and ≥40 Gy group ( n= 140). The intracranial progression-free survival (iPFS) and overall survival (OS) were compared betweentwo groups. According to the number of brain metastases, GPA score, KPS score, chemotherapy and targeted therapy, the prognosis of different doses of WBRT was further analyzed. Results:The median iPFS and OS of all patients were 6.9 months and 11.8 months, respectively. Univariate survival analysis: the 1-year iPFS and 1-year OS between two groups were 22.5% and 25.4%( P=0.430) and 41.1% and 46.4%( P=0.068), respectively. Multivariate survival analysis: different doses of WBRT were not associated with the improvement of iPFS and OS; independent factors influencing iPFS included local boost, gender, number of brain metastases, chemotherapy and targeted therapy; independent factors influencing OS included gender, number of brain metastases, chemotherapy and targeted therapy. Subgroup analysis: in patients with KPS≥90, the 1-year iPFS and OS of patients with WBRT ≥ 40 Gy were seemingly better than those of their counterparts with 30-39 Gy, but the difference was statistically significant only in OS ( P=0.047), the difference was not statistically significant in iPFS ( P=0.068); in patients with chemotherapy, the 1-year iPFS and OS of patients with WBRT≥40 Gy were better than those of their counterparts with 30-39 Gy ( P=0.017, P=0.012); in patients with targeted therapy, the 1-year iPFS and OS in the WBRT≥40 Gy group were better than those in the 30-39 Gy group ( P=0.012, P=0.045). Conclusions:The 30-39 Gy may be the appropriate dose of WBRT for NSCLC patients with brain metastases. WBRT≥40 Gy does not bring more benefits. WBRT≥40 Gy may benefit NSCLC patients with brain metastases with high KPS score or active systemic therapy.

Objective:To explore the optimal local treatment pattern of supraclavicular lymph node in breast cancer patients with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM).Methods:Clinical data of 128 breast cancer patients with sISLM admitted to the Fourth Hospital of Hebei Medical University from 2010 to 2015 were retrospectively analyzed. Among them, 68 cases were treated with supraclavicular lymph node dissection combined with radiotherapy, and 60 cases received radiotherapy alone. The locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were statistically compared between two groups.Results:Univariate analysis demonstrated that the 5-year LRFS, DMFS, PFS and OS did not significantly differ between two groups (all P>0.05). Multivariate analysis revealed that the local treatment pattern of supraclavicular lymph node was an independent prognostic factor for the 5-year DMFS, PFS and OS (all P<0.05). Subgroup analysis showed that when radiotherapy alone was performed, the 5-year OS of patients in the supraclavicular region radiation dose of>50 Gy group were significantly better than that in the 50 Gy group ( P=0.047). When supraclavicular lymph node dissection combined with radiotherapy was delivered, if the number of dissection was less than 10, the 5-year LRFS, DMFS, PFS, OS of patients in the>50 Gy group were all better than those in the 50 Gy group numerically without statistical significance (all P>0.05). If the number of dissection was ≥10, the 5-year LRFS, DMFS, PFS, OS in the 50 Gy group were better than those in the>50 Gy group numerically, whereas significant difference was only found in the 5-year DMFS ( P=0.028). Conclusions:Supraclavicular lymph node dissection combined with radiotherapy may be the optimal local treatment pattern for supraclavicular lymph node. When radiotherapy alone is performed, a radiation boost to the supraclavicular region may improve OS. When supraclavicular lymph node dissection combined with radiotherapy is performed, if the degree of dissection is low, a radiation boost to the supraclavicular region may bring clinical benefits. However, if the degree of dissection is high, a radiation boost to the supraclavicular region may not bring significant clinical benefits.

Objective:To evaluate the effect of prophylactic irradiation of internal mammary lymph nodes in patients with breast cancer in this Meta-analysis.Methods:CNKI, Wanfang Medical network, CBM, PubMed, EMBASE and Web of Science were searched by computer. The controlled clinical studies comparing whether or not internal mammary lymph node irradiation as an intervention were included and the quality of the included literature was evaluated according to Newcastle-Ottawa Scale (NOS). RevMan 5.3 software and Stata 14 software were used for Meta-analysis.Results:A total of 11 original articles were included, and 13 181 patients were included for Meta-analysis. There was no statistically significant difference in the overall survival (OS) between patients with and without internal mammary lymph node irradiation ( P=0.490). The subgroup analysis using the date of treatment and the degree of risk in the enrolled population as criteria showed that 5-year OS was significantly increased after internal mammary area irradiation in high-risk stage Ⅱ-Ⅲ patients (N+ , T 3-T 4 stage) with the date of treatment of after 2000( P=0.003, 0.006). Compared with patients without internal mammary area irradiation, internal mammary irradiation significantly increased the 5-year disease-free survival (DFS)( P<0.001). Conclusion:Under the modern radiotherapy technology, internal mammary lymph node irradiation improves the DFS of patients, and may bring OS benefits to high-risk stage Ⅱ-Ⅲ breast cancer patients (N+ , T 3-T 4 stage).

Objective To analyze the failure patterns and prognostic factors of radical surgery in patients with T1-4N0-1M0 thoracic esophageal squamous cell carcinoma (TESCC),and the implications for the target area design of postoperative therapy.Methods We retrospectively analyzed 1 191 patients with TESCC who underwent radical surgery at our institution.The failure patterns,the prognostic factors,as well as the effects of lesion locations and N stage on the failure patterns were analyzed.Results The thoracic-region recurrence rate and the distant metastasis rate was 31.7％ and 16.4％ in all patients.The multivariate analysis showed that the lesion locations,the degree of inflammatory adhesion,T staging,N staging and the rate of lymph nodes metastasis were independent factors affecting the regional recurrence (P ＜ 0.05).Gender,tumor differentiation and the rate of lymph nodes metastasis were independent factors affecting distant metastasis (P ＜ 0.05).The intrathoracic lymph nodes recurrence rate of upper/middle TESCC was significantly higher than that of the lower TESCC (x2 =6.179,P =0.046),while the abdomen lymph nodes recurrence rate of the lower was significantly higher than that of upper/middle TESCC (x2 =15.853,P ＜ 0.05).The recurrence rate and distant metastasis rate of stage N1 patients were significantly higher than that of N0 patients (x2 =7.764-56.495,P ＜ 0.05).The abdomen lymph nodes recurrence rate of stage N1 patients was significantly higher than that of N0 in upper TESCC (x2 =7.905,P ＜0.05).The supraclavicular and intrathoracic lymph nodes recurrence rates of stage N1 patients were significantly higher than that of N0 patients in middle TESCC (x2 =12.506,18.436,P ＜ 0.05).The supraclavicular lymph nodes,anastomosis and abdomen lymph node recurrence rates of stage N1 were significantly higher than that of N0 patients in lower TESCC (x5 =5.272,4.878,18.006,P ＜ 0.05).The anastomotic recurrence rate of stage T3+4 was higher than that of T1+2 in middle/lower TESCC (x2 =4.341,7.154,P ＜ 0.05),and the abdominal lymph nodes recurrence rate of stage T3 +4 was higher than that of T1 +2 in lower TESCC (x2 =5.366,P ＜ 0.05).Conclusions The lymphatic drainage regions for postoperative radiotherapy (PORT) are selective.We suggest that abdominal lymph nodes drainage area should be noted for the stage N1 patients with upper TESCC,and the supraclavicular lymph nodes drainage area should be noted for the N1 patients with lower TESCC.In addition,the anastomosis is suggested to be included in PORT target area for stage T3/T4 middle/lower TESCC patients.

Objective To compare the prognosis of patients with squamous cell carcinona of the upper thoracic esophagus after radical resection with and without postoperative chemoradiotherapy (POCRT).Methods From January 2007 to December 2011,168 patients with upper thoracic esophageal carcinoma who were treated in the Fourth Hospital of Hebei Medical University were retrospectively included in this study.According to the different treatment method,they were divided into simple surgery group (86 cases) and POCRT group (82 cases) respectively.Based on SPSS statistical software,the group data composition,prognostic analysis and multivariate prognostic analysis were performed by x2 test,Log-rank method and Cox regression model,respectively.Results The 1,3,5 year-survival rate,recurrence rate and distant metastasis rate were 83.9％,52.4％,43.5％,26.5％,40.8％,43.4％ and 5.3％,11.4％,16.9％,respectively.The result of multivariate analysis showed that gender,T stage,N stage and treatment method were independent prognostic factors of overall survival (P =0.020,0.008,0.005,0.000);N staging and treatment method were the independent prognostic factors of local/regional recurrence (P =0.001,0.003);differentiation and T staging were the independent prognostic factors of distant metastasis (P =0.045,0.020).The intrathoracic regional recurrence rate of operation only group and POCRT group patients were 44.2％ (38/86) and 29.3％ (24/82) respectively,where the difference was statistically significant (x2 =7.110,P ＜ 0.05).The rate of metastasis were 19.8％ (17/86) and 13.4％ (11/82) respectively without significant difference (P ＞0.05).Conclusions The recurrence rate of patients with upper thoracic esophageal squamous cell carcinoma after radical resection was still high.Postoperative chemoradiotherapy can improve the overall survival rate and reduce the recurrence rate,but whether it can reduce the patient's distant metastasis rate needs further study.

Objective To analyze the risk factors for abdominal lymph node recurrence after radical surgery in patients with middle thoracic esophageal squamous cell carcinoma (TE-SCC),and to design the target volume for postoperative radiotherapy based on the results.Methods A retrospective study was performed among 913 patients with middle TE-SCC undergoing radical surgery who were admitted to our hospital from 2007 to 2012.Influencing factors were analyzed for abdominal lymph node recurrence after treatment.The efficacy was compared between different treatment methods in the high-risk population.Comparison of categorical data was made by chi-square test.The overall survival rates (OS) were calculated by the Kaplan-Meier method and analyzed by the univariate log-rank analysis.The influencing factors for abdominal lymph node recurrence were analyzed by the multivariate logistic regression equation.Results After treatment,37 patients had abdominal lymph node recurrence,yielding a recurrence rate of 4.1％.A total of 53 recurrent sites were found.The univariate analysis showed that no/low differentiation,pT3+4 stage,no less than 3 positive postoperative lymph nodes,and positive postoperative abdominal lymph nodes were influencing factors for abdominal lymph node recurrence (P =0.032,0.001,0.009,0.000).The multivariate regression analysis showed that pathological T staging and positive postoperative abdominal lymph nodes were influencing factors for abdominal lymph node recurrence (P=0.011,0.000).For patients with pT3+4 stage disease and positive postoperative abdominal lymph nodes,postoperative radiotherapy improved OS and local control rates but failed to reduce the distant metastasis-free rate.Conclusions T staging and positive postoperative abdominal lymph nodes are important risk factors for abdominal lymph node recurrence after radical surgery in patients with middle TE-SCC.Postoperative adjuvant therapy is recommended for patients with pT3+4 stage disease and positive postoperative abdominal lymph nodes.

Objective To compare the efficacy between different modalities in the treatment of positive lymph nodes after radical resection for squamous cell carcinoma of thoracic esophagus(TESCC),and to explore the best treatment mode. The Kaplan?Meier method was used to calculate survival rates. The log-rank test and Cox model were used for univariate and multivariate prognostic analyses,respectively. Methods A retrospective analysis was performed among 548 patients with TESCC who were admitted to our hospital and had positive lymph nodes after radical resection. The efficacy of different treatment methods was evaluated. Propensity scores(PSM)were used to make 1-to-1 patient matching between different treatment groups to further analyze and figure out the best treatment model for patients. The Kaplan?Meier method was used to calculate the overall survival(OS)and disease-free survival(DFS)rates. The log-rank test was used for survival analysis and univariate prognostic analysis. The Cox regression model was used for multivariate prognostic analysis. Results In all patients,the 1-,3-,and 5-year OS rates were 79.9%, 38.1% and 28.5%,respectively,while the 1-,3-,and 5-year DFS rates were 68.5%,39.8% and 32.5%, respectively. After 1-to-1 matching based on PSM,there were no differences in general clinical pathological data between the four groups. After PSM,there were significant differences in 1-,3-,and 5-year OS and DFS rates between the surgery alone group,the postoperative radiotherapy group,the postoperative chemotherapy group,and the postoperative chemoradiotherapy(POCRT)group(P=0.000,0.000).There were significant differences in OS and DFS rates between patients with stage N1,N2,and N3disease(P=0.000,0.000).The result of the Cox multivariate analysis showed that treatment method and N staging were two independent prognostic factors for OS and DFS(P=0.001,0.000,0.025,0.016). Conclusions Patients with positive lymph nodes after radical resection for TESCC have a poor prognosis. Moreover,the prognosis becomes worse with the increase in metastatic lymph nodes. POCRT may improve the survival in those patients. Prospective studies are needed to further confirm those conclusions.

Objective To investigate the failure model of patients with stage pN0 thoracic esophageal squamous cell carcinoma (TESCC) after surgery alone and to discuss the feasibility of postoperative radiotherapy.Methods A retrospective analysis was performed on 473 patients with TESCC who received surgery alone from January 2007 to December 2010.The feasibility of adjuvant radiotherapy for pN0 TESCC patients was investigated through the failure model of postoperative patients.Results Of all patients,there were 57 cases with chest-regional recurrence (12.1％),most of which occurred in the mediastinal lymph nodes(52 case).There were 42 (8.9％) patients were identified as distant metastasis (DM),of which 13 cases were found to have both local recurrence and DM,and the total failure rate was 20.9％.The chest-regional recurrence rate of upper TESCC was statistically significantly higher than middle and lower (x2 =7.469,P ＜ 0.05),but DM rate had no statistically significant difference (P ＞ 0.05).The chest-regional recurrence rate and DM rate of the advanced T stage were significantly higher than those of the early T stage(x2 =10.247,7.886,P ＜ 0.05).The result of univariate analysis showed that disease site,the degree of adhesion,postoperative stump were significant factors of chestregional recurrence rate (x2 =14.232,9.486,7.546,P ＜ 0.05).Gender,smoking and preoperative weight loss ≥5 kg significantly influenced DM (x2 =10.823,10.275,6.065,P ＜ 0.05).In addition,the T stage was the significant influence factor of chest-regional recurrence and DM(x2 =15.994,12.885,P ＜0.05).The result of multivariate analysis showed that T stage and postoperative stump were independent factors of chest-regional recurrence (P ＜ 0.05).Smoking was an independent factor of DM (P ＜ 0.05).Conclusions There was a high rate of chest-regional recurrence in patients with stage pN0 TESCC who received surgery alone.Postoperative radiotherapy was recommended for patients with upper TESCC,advanced T stage,severe local adhesion,positive margin in and postoperative stump.Male,smoking and preoperative weight loss≥5 kg were associated with higher DM rate.