[Clinicopathological features of patients with RET fusion-positive non-small cell lung cancer].

Objective: To investigate the clinicopathological features, treatment and prognosis of patients with RET fusion positive non-small cell lung cancer (NSCLC). Methods: A total of 1 089 NSCLCs were retrieved at Affiliated Hospital of Jiangnan University from August 2018 to April 2020. In all cases, multiple gene fusion detection kits (fluorescent PCR method) were used to detect the gene status of RET, EGFR, ALK, ROS1, KRAS, BRAF and HER2; and immunohistochemical method was used to detect the expression of PD-L1 and mismatch repair related proteins. The correlation between RET-fusion and patients' age, gender, smoking history, tumor stage, grade, pathologic type, and PD-L1, mismatch repair related protein expression was analyzed. Results: There were 22 cases (2.02%) detected with RET fusion-positive in 1 089 NSCLC patients, in which 11 males and 11 females; and the median age was 63.5 years. There were 20 adenocarcinomas, including 11 acinar predominant adenocarcinoma (APA), five solid predominant adenocarcinoma (SPA) and four lepidic predominant adenocarcinoma (LPA); There were one case each of squamous cell carcinoma (non-keratinizing type) and sarcomatoid carcinoma (pleomorphic carcinoma). There were 6 and 16 patients with RET fusion-positive who were in stage Ⅰ-Ⅱ and Ⅲ-Ⅳ respectively, and 16 cases with lymph node metastasis, 11 cases with distant metastasis. Among RET fusion-positive cases, one was detected with HER2 co-mutation. The tumor proportion score of PD-L1≥1% in patients with RET fusion positive lung cancer was 54.5% (12/22). Defects in mismatch repair protein expression were not found in patients with RET fusion positive NSCLC. Four patients with RET fusions positive (two cases of APA and two cases of SPA) received pratinib-targeted therapy, and two showed benefits from this targeted therapy. Conclusions: The histological subtypes of RET fusions positive NSCLC are more likely to be APA or SPA. RET fusion-positive NSCLC patients are associated with advanced clinical stage, lymph node metastases, and they may benefit from targeted therapy with RET-specific inhibitors.

[Study on efficacy, recurrence rate and related risk factors between ablation index and contact force guided radiofrequency ablation of paroxysmal atrial fibrillation in elderly patients].

Objective: To compare the efficacy, safety and recurrence rate between ablation index (AI) and contact force (CF) guided radiofrequency ablation of paroxysmal atrial fibrillation in elderly patients. Methods: Elderly patients (age ≥60 years) with paroxysmal atrial fibrillation who received radiofrequency ablation for the first time at Department of Cardiology, Beijing Friendship Hospital from April 2018 to April 2019 were enrolled. Patients were divided into 2 groups: AI-group (n=40) and CF group (n=37) depending on their ablation methods. Follow-up was performed until 1 year post the procedure, and efficacy related indexes like first-pass pulmonary vein isolation (PVI) rate, ablation duration, operation duration and major complications were compared between 2 groups. The recurrence rates between 2 groups and related risk factors after radiofrequency ablation were analyzed. Results: A total of 77 patients [mean age (68.5±6.4) years, 40 were male] were enrolled at last. In AI guided patients, frequency of first-pass PVI rate was higher [52.5%(21 cases) vs 29.7%(3 cases), P=0.011] with a shorter ablation duration [(24.5±1.7) min vs (33.7±2.2) min, P<0.001] and operation duration [(136.6±6.1) min vs (139.7±7.4) min, P=0.048] compared with CF guided group. At 1 year follow-up, AI group showed an amendatory recurrence rate in Kaplan-Meier analysis (22.5% vs 40.5%,log-rank P=0.048). Multivariate Cox regression analysis showed that CF guided ablation (HR=3.272,95%CI:1.319-8.114,P=0.011), enlarged anteroposterior diameter of the left atrium (HR=4.233,95%CI:1.511-11.862,P=0.006) and complicated with coronary heart disease (HR=4.829,95%CI:1.399-16.666,P=0.013) were independent risk factors for recurrence of atrial fibrillation in elderly patients. Conclusions: Compared with CF guided ablation, radiofrequency ablation of paroxysmal atrial fibrillation in elderly patients guided by AI showed a higher first-pass PVI rate, shorter procedure duration of both ablation time and total operation time, meanwhile a lower recurrence rate. Further analysis revealed that different ablation alternation (AI or CF), enlarged anteroposterior diameter of left atrium, and complicated with coronary heart disease are independent risk factors for recurrence after radiofrequency ablation of atrial fibrillation in elderly patients.

Short-term efficacy of surgical treatment of secondary hyperparathyroidism.

OBJECTIVE: We wished to explore short-term efficacy of surgical treatment of secondary hyperparathyroidism in patients with the end-stage renal disease. The treatment methods were subtotal or total parathyroidectomy, or total parathyroidectomy and autotransplantation. PATIENTS AND METHODS: 63 patients with secondary hyperparathyroidism were randomly divided into three groups which were respectively treated with subtotal parathyroidectomy (SPTX group), total parathyroidectomy (TPTX group), or total parathyroidectomy and autotransplantation (TPTX+AT group). The surgical outcomes included operating time, transoperative bleeding volume, length of stay, and cost of hospitalization. In addition, complication (e.g., postoperative wound infection, hematoma, hypocalcemia in perioperative period) rates were compared among groups. Blood levels of calcium and parathyroid hormone were assessed before the surgery, and 1 day, 1 months, 3 months and 6 months after the surgery. The follow-up period comprised 6 months. RESULTS: Surgical outcomes were the lowest in SPTX group and the highest in in TPTX+AT group. There were no significant differences among groups in treatment efficacy. Complication rates were also comparable among the three groups. The occurrence of hypocalcemia was the lowest in SPTX group (p < 0.05 vs. other groups). However, postoperative relapse rate was the highest in this group (p < 0.05 vs. other groups). There were no correlations between the levels of blood calcium and PTH preoperatively and postoperatively. CONCLUSIONS: Appropriate surgical treatment is selected in accordance with the patient's condition and willingness, with the attention paid to the prevention of hypocalcemia.

Studies on expression of p14ARF and MDM2 in human thyroid neoplasms.

AIM: We sought to evaluate the expression and clinical significance of p14ARF and MDM2 proteins in thyroid neoplasm. METHODS: Immunohistochemical streptavidin-peroxidase (S-P) method was used to detect the expression of p14ARF and MDM2 proteins in 78 cases of papillary thyroid carcinoma (PTC), 34 cases of papillary thyroid microcarcinoma (PTMC) and 45 cases of thyroid adenoma. RESULTS: The expression of p14ARF and MDM2 protein differed significantly (P<0.01) among three group. The positivity rate of p14ARF protein in PTC was significantly lower than that in thyroid adenoma (P=0.002) and PTMC (P=0.008). While the positivity rate of MDM2 protein in PTC was significantly higher than that in thyroid adenoma (P=0.000) and PTMC (P=0.009). There was a significant correlation found between the expressions of p14ARF and MDM2 proteins in PTC (P=0.013) and PTMC (P=0.012). Also, a significant correlation was found between p14ARF protein expression and lymph node metastasis in PTC (P=0.011). CONCLUSION: It was concluded that p14ARF and MDM2 proteins might be involved in the induction and development of PTC and PTMC whereas p14ARF also had diagnostic value in determining the biological behavior of PTC.

Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits.

After injury, inflammation, or degeneration, articular cartilage has limited self-repair ability. We aimed to explore the feasibility of repair of articular cartilage defects with tissue-engineered cartilage constructed by acellular cartilage matrices (ACMs) seeded with adipose-derived stem cells (ADSCs). The ADSCs were isolated from 3-month-old New Zealand albino rabbit by using collagenase and cultured and amplified in vitro. Fresh cartilage isolated from adult New Zealand albino rabbit were freeze-dried for 12 h and treated with Triton X-100, DNase, and RNase to obtain ACMs. ADSCs were seeded in the acellular cartilaginous matrix at 2x10(7)/mL, and cultured in chondrogenic differentiation medium for 2 weeks to construct tissue-engineered cartilage. Twenty-four New Zealand white rabbits were randomly divided into A, B, and C groups. Engineered cartilage was transplanted into cartilage defect position of rabbits in group A, group B obtained ACMs, and group C did not receive any transplants. The rabbits were sacrificed in week 12. The restored tissue was evaluated using macroscopy, histology, immunohistochemistry, and transmission electron microscopy (TEM). In the tissue-engineered cartilage group (group A), articular cartilage defects of the rabbits were filled with chondrocyte-like tissue with smooth surface. Immunohistochemistry showed type II-collagen expression and Alcian blue staining was positive. TEM showed chondrocytes in the recesses, with plenty of secretary matrix particles. In the scaffold group (group B), the defect was filled with fibrous tissue. No repaired tissue was found in the blank group (group C). Tissue-engineered cartilage using ACM seeded with ADSCs can help repair articular cartilage defects in rabbits.

Expression features of CXCR5 and its ligand, CXCL13 associated with poor prognosis of advanced colorectal cancer.

OBJECTIVE: CXCL13 plays a unique role in the trafficking and homing of B1 cells associated with its cognate receptor, CXCR5. The CXCR5-CXCL13 axis has been previously demonstrated to be a poor prognosis factor in malignancies. However, the clinical significance of the CXCR5-CXCL13 expression in colorectal cancer carcinoma (CRC) remains unclear. The aim of this study was to investigate the CXCR5-CXCL13 expression in CRC and determine its correlation with the progression and prognosis of the tumor. PATIENTS AND METHODS: A total of 144 paraffin-embedded specimens with advanced colon cancer were assessed for CXCR5 and CXCL13 by immunohistochemistry. Patients' long-term survival was also monitored. There were significant differences in lymph node metastasis (p = 0.0066), neural invasion (p = 0.0061) and neural invasion (p = 0.0001) between high and low expression of CXCR5. RESULTS: There were significant differences in distant metastasis (p = 0.0261), TNM stage (p = 0.0409), differentiation (p < 0.0001) and neural invasion of the CXCL13. Both CXCR5 and CXCL13 was associated with poor correlation with the overall survival (OS) and relapse-free survival (RFS). CONCLUSIONS: Our data suggest that the CXCR5 and CXCL13 may play a crucial role in the development, metastasis and relapse of advanced colon cancer. They can be used as prognostic markers of colon cancer in clinical practice.

A unique surface-initiated property of nanoparticles and application for the synthesis of hybrid organic-inorganic nanoparticles.

We report a unique property of nanoparticles to initiate acrylic acid and acrylamide solution polymerization under low air pressure conditions. This property could be applied to synthesize a wide variety of hybrid organic-inorganic nanoparticles, which hold great promise for use in nanophotonics, catalysis, and medical applications.

Role of Sphk1 in the malignant transformation of breast epithelial cells and breast cancer progression.

BACKGROUND: The ojective of the following study is to investigate the role of sphingosine kinase 1 (Sphk1) in the malignant transformation of breast epithelial cells and breast cancer progression and its mechanism. MATERIALS AND METHODS: Immunohistochemistry was performed to detect Sphk1 and E-cadherin (E-cad) in resected breast samples. Sphk1 was transfected in normal human breast epithelial cell line (MCF-10A) by Lentivirus and silenced in breast cancer cell line (MCF-7) using small interfering ribonucleic acid. The effect of tumor necrosis factor alpha (TNF-α) and/or N, N-dimethylsphingosine (DMS) on the Sphk1 and E-cad expression, MCF-10A cell proliferation and invasion was investigated. Real time-polymerase chain reaction and western-blot was used to detect messenger ribonucleic acid and protein. Cell counting kit-8 and transwell were used to measure cell proliferation and invasion. RESULTS: Sphk1 was positive expression in 114 breast tumors (75.50%) but negative in fibroadenomas. The expression of E-cad and Sphk1 were negatively correlated and E-cad (-)/Sphk1 (+) carriers showed higher ratio of axillary lymph node metastasis than E-cad (+)/Sphk1 (-) carriers. Overexpression of Sphk1 in MCF-10A reduced E-cad expression and improved cell proliferation and invasion, but knockdown of Sphk1 in MCF-7 decreased cell proliferation and invasion. TNF-α increased Sphk1 expression, enhanced the ability of Sphk1 in decreasing E-cad expression, which could be blocked by DMS. TNF-α promoted MCF-10A cell proliferation and invasion. CONCLUSION: Sphk1 plays an important role in the malignant transformation of breast epithelial cells and modulates breast cancer metastasis through the regulation of E-cad expression. TNF-α can up-regulate Sphk1 expression and reduce E-cad expression through Sphk1, which can be blocked by DMS. TNF-α/Sphk1/E-cad pathway may be a newly discovered pathway and plays an important role in tumorigenesis and metastasis.