[Efficacy and prognostic analysis of 125I brathytherapy combined with chemotherapy for pediatric parameningeal rhabdomyosarcoma].

Objective: To analyze the efficacy and prognostic factors in children with parameningeal rhabdomyosarcoma (PMRMS) treated by 125I brachytherapy combined with chemotherapy. Methods: A retrospective analysis of the clinical data of 33 pediatric patients treated with 125I brachytherapy combined with chemotherapy in Peking University Stomatological Hospital from July 2013 to October 2018 was carried out to analyze the efficacy and prognostic factors. Results: Among the 33 patients, 19 were males and 14 were females; the median age was 4 years old (1-12 years old). There were 17 cases with embryonic type, 9 cases with alveolar type, and 7 with undifferentiated type; 26 cases with original PMRMS, and 7 cases with recurrent PMRMS. The tumors occurred in subtemporal-mastoid area in 15 patients, while nasopalatine-paranasal area in 6 cases, and parapharyngeal-submandibular area in 12 cases. There were 28 patients in IRS Ⅲ, and 5 patients in IRS Ⅳ. As for the risk level, 28 cases were in the middle-risk group and 5 cases in the high-risk group. The median follow-up time was 52 months. The 1, 3, and 5-year local control rates were 87.9%, 58.6%, and 49.9%, and the 1, 3, and 5-year survival rates were 93.8%, 60.5%, and 47.5%, respectively. The 5-year local control rate and 5-year survival rate of 12 patients with the tumor in the parapharyngeal-submandibular area were 91.7% and 100%, respectively. The 5-year local control rate and 5-year survival rate of the 6 patients with tumor in the nasopalatine-paranasal area were both 83.3%. The 3-year local control rate and 3-year survival rate of the 15 patients with tumor in the subtemporal-mastoid area were 17.5% and 21.4%. The multivariate survival analysis using Cox proportional risk regression model showed that the tumor located in the subtemporal-mastoid area was an independent risk factor affecting the 5-year overall survival rate (HR=38.40, 95%CI: 4.87-302.52, P=0.001). Within 3 months after 125I seed implantation, the incidence of acute radiotherapy adverse reactions in all patients was 84.8% (28/33). Twenty-one patients (63.6%) had a grade 1 acute radiotherapy reaction, and 7 cases (21.2%) had a grade 2 acute radiotherapy reaction. No acute radiotherapy adverse reactions of grade 3 or 4 occurred. Three months after 125I seed implantation, the adverse reactions were significantly alleviated, and no adverse reactions of grade 3 or above such as skin ulcer or salivary gland fibrosis occurred, and no serious cranio-maxillofacial deformities occurred. Conclusions: 125I seed brachytherapy combined with chemotherapy has a definite clinical effect in the treatment of children with parameningeal rhabdomyosarcoma. The prognosis of rhabdomyosarcoma in the parapharyngeal-submandibular area and nasopalatine-paranasal area is better than that in the subtemporal-mastoid area.

[Correlation between serum CCL20 level and disease severity in patients with rheumatoid arthritis].

Objective: To investigate the correlation between serum CCL20 level and disease severity in patients with rheumatoid arthritis (RA). Methods: From July 2018 to July 2019, a cross-sectional study was conducted in the Department of Rheumatology and Immunology, the Third Affiliated Hospital of Southern Medical University. The observation group consisted of 105 outpatients and inpatients diagnosed with RA, while the control group was 90 healthy people with age and gender matched physical examination in the Third Affiliated Hospital of Southern Medical University. According to Steinbroker classification, RA patients were divided into Steinbroker grade 2 group (n=35), Steinbroker grade 3 group (n=38) and steinbroker grade 4 group (n=32); according to DAS28 score, RA patients were divided into remission group (DAS28<2.6)(n=39), mild active group (DAS28 2.6-3.2)(n=25), moderate active stage group (DAS28 3.2-5.1)(n=20) and severe active stage group (DAS28 ≥ 5.1)(n=21). The levels of chemokine ligand 20 (CCL20), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were detected by ELISA. The levels of CCL20 in each group were compared, and the correlation between CCL20 and other indicators was analyzed. The receiver operating characteristic (ROC) curve of CCL20 in diagnosis of RA was analyzed to explore the correlation between CCL20 and disease severity of RA patients. Results: Compared with the normal control group, the serum CCL20 level in RA patients was significantly increased [(48.1±16.7) pg/ml vs (17.6±5.9) pg/ml, t=19.39, P<0.001]. In addition, serum CCL20 in steinbroker grade 4 group was significantly higher than that in Steinbroker grade 3 group [(59.5±10.1) pg/ml vs (47.4±17.5) pg/ml, t=3.472, P<0.001], and the serum CCL20 level in steinbroker grade 3 group was significantly higher than that in steinbroker grade 2 group [(47.4±17.5) pg/ml vs (38.4±14.6) pg/ml, t=2.370, P<0.001], CCL20 level in steinbroker grade 2 group was significantly higher than that in normal control group [(38.4±14.6) pg/ml vs (17.6±5.9) pg/ml, t=7.738, P<0.001]. In addition, serum CCL20 level was significantly positively correlated with steinbroker score (r=0.505, P<0.001); CCL20 level in active RA patients was significantly higher than that in remission RA patients [(57.2±13.2) pg/ml vs (32.7±8.9) pg/ml, t=10.31, P<0.001]. The serum CCL20 level in severe activity group was significantly higher than that in moderate activity group [(60.6±10.9) pg/ml vs (51.7±16.2) pg/ml, t=0.212, P=0.040], and the serum CCL20 level in moderate activity group was significantly higher than that in mild activity group [(51.7±16.2) pg/ml vs (40.5±18.6) pg/ml, t=0.217, P=0.037]. In addition, there was a significant positive correlation between serum CCL20 level and DAS28 score (r=0.451, P<0.001). In addition, serum CCL20 level was positively correlated with serum CRP (r=0.332, P<0.001). According to the ROC curve, the specificity of steinbroker grade 2 group was 0.53, and the sensitivity was 0.74, AUC was 0.659; the sensitivity of steinbroker grade 3 group was 0.78, and the specificity was 0.69, AUC was 0.734; the sensitivity of mild vs medium stage was 0.64, and the specificity was 0.70, AUC was 0.699; the sensitivity of medium stage vs severe stage was 0.57, and the specificity was 0.68,AUC was 0.678. Conclusion: Serum CCL20 level in RA patients is significantly increased and positively correlated with disease severity, which may be used as a marker to observe and evaluate the progression of RA.

[Application of the submandibular gland for management of stage 3 medication-related osteonecrosis of the mandible].

Objective: To summarize the clinical outcomes of reconstruction plate fixation combined with submandibular gland translocation (A) or reconstruction plate fixation combined with submental island flap and submandibular gland (B) for mandibular stage-3 medication-related osteonecrosis of the jaw (MRONJ). Methods: The clinical data of the patients with stage-3 mandibular MRONJ treated with one of the above mentioned procedures from September 2014 to December 2020 in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, were retrospectively reviewed. The clinical data included the general data of the patients, the initial mucosal healing rate at the time of 2 weeks postoperatively and follow-up, and the occurrence of complications. Results: A total of 40 patients were treated, including 17 males and 23 females, aged (64.6±8.9) years. Among the patients, 33 were treated with operation A and 7 with operation B. The initial mucosal healing rate was 90% (36/40). Plate fracture occurred in 4 patients. The mean length of the mandibular bony defect was (4.5±1.4) cm (ranged from 2.1 to 8.0 cm). Conclusions: For management of stage-3 mandibular MRONJ, reconstruction plate fixation combined with submandibular gland translocation or with submental island flap and submandibular gland might be one of the effective and reliable options.

[The expression and significance of IGF1R-Ras/RAGE-HMGB1 pathway in colorectal cancer patients with type 2 diabetes mellitus].

Objective: To investigate the expression of IGF1R-Ras and RAGE-HMGB1 signaling pathways in colorectal cancer patients with type 2 diabetes mellitus and their significance. Methods: The resected cancer tissues were obtained from 59 patients with colorectal cancer (CRC), including 29 patients with type 2 diabetes mellitus (CRC/DM group) and 30 with CRC alone (CRC group). The expressions of IGF1R, Ras, RAGE and HMGB1 in cancer tissues were detected by immunohistochemistry. The differences between the two groups were compared and the relationship between the expression and clinicopathological characteristics was analyzed. Results: In CRC/DM group, the positive rates of IGF1R and Ras were both 65.5% (19/29), and 51.7% (15/29) patients had IGF1R+ Ras+ immunophenotype, which were significantly higher than those in CRC group [33.3% (10/30), 36.7% (11/30) and 20.0% (6/30); P=0.013, 0.027 and 0.011, respectively]. The expression of IGF1R and Ras in CRC / DM group was positively correlated (r=0.479, P=0.017). The positive rate of RAGE expression in CRC group and CRC/DM group was 70.0% (21/30) and 72.4% (21/29) respectively, and the positive rate of HMGB1 expression was 46.7% (14/30) and 58.6% (17/29) respectively, neither was observed with significant difference (P=0.358 and 0.838). However, the proportion of patients with RAGE+ HMGB1+ immunophenotype in CRC/DM group [55.2% (16/29)] was higher than that in CRC Group [26.7% (8/30)] which was statistically significant (P=0.026), and the expression of both proteins was positively correlated in CRC/DM group (r=0.578, P=0.003). The clinicopathological analysis showed that in both groups the expression of IGF1R, Ras, RAGE and HMGB1 had no correlation with the sex, age, differentiation degree, tumor length, T stage and lymph node metastasis (P>0.05). Conclusion: Both IGF1R-Ras and RAGE-HMGB1 pathways may be involved in the oncogenesis of colorectal cancer in patients with type 2 diabetes.

Analyzing risk factors for recurrence of developmental coxa vara after surgery.

PURPOSE: To evaluate the risk factors for developmental coxa vara (DCV) recurrence following valgus osteotomy of the proximal femur. METHODS: We retrospectively reviewed records of 32 DCV patients (46 hips) treated surgically (2005 to 2012). Recurrence-related factors, including age at initial surgery, side, sex, fixation methods, diagnosis of coxa vara, premature capital femoral physeal closure and postoperative Hilgenreiner epiphyseal (HE) angle, head-shaft (HS) angle, medial femoral offset and posterior slope angle (PSA) were analyzed. RESULTS: At 4.7-year mean follow-up, 12 hip deformities recurred (26%). Postoperative HE angle > 41° and negative offset were statistically significant univariate and multivariate risk factors for the deformity recurrence. Increased PSA was common preoperatively, which accounted for 59% of hips. Postoperative PSA > 20° was associated with a high recurrence rate in the univariate analysis. Age was another univariate risk factor for the recurrence. Recurrence rate was 52% in the < 6.5-year age group versus 4% in the > 6.5-year age group. Other factors were not statistically significantly related to recurrence. CONCLUSION: DCV is a 3D deformity. To prevent recurrence, HE angle should be restored to < 41° in the coronal plane. Sagittal malalignment (abnormal PSA) should be corrected concurrently, so that, the direction of surgical correction is along the true deformity plane. During valgus osteotomy, the distal fragment should be lateralized to maintain a normal mechanical axis. LEVEL OF EVIDENCE: IV.

EBV-miR-BART7-3p promotes the EMT and metastasis of nasopharyngeal carcinoma cells by suppressing the tumor suppressor PTEN.

The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p enhanced cell migration/invasion in vitro, cancer metastasis in vivo, and particularly the EMT characterized by loss of epithelial markers and gain of mesenchymal features in NPC cells. Furthermore, mechanistic studies disclosed that EBV-miR-BART7-3p targeted a major human tumor suppressor PTEN, modulating PI3K/Akt/GSK-3ß signaling and eventually leading to the high expression and nuclear accumulation of Snail and ß-catenin, which favor EMT. Knockdown of PTEN could phenocopy the effect of EBV-miR-BART7-3p, whereas re-expression of PTEN resulted in a phenotypic reversion. Moreover, these findings were supported by an observation of an EBV-positive cell model in which silencing of endogenous EBV-miR-BART7-3p partially attenuated cell migration/invasion and altered EMT protein expression pattern via reverting PI3K/Akt, Snail and ß-catenin expression. Thus, this study suggests a novel mechanism by which EBV-miR-BART7-3p modulates the EMT and metastasis of NPC cells, and a clinical implication of EBV-miR-BART7-3p as a potential biomarker or therapeutic target.