Purpose: The purpose of this study is to examine the effectiveness of introducing both rituximab (RTX) and ¹³¹I for active Graves' ophthalmopathy (GO) with hyperthyroidism. Methods: In total, 217 patients suffering from active GO with hyperthyroidism were included in this research. All subjects were randomly assigned to 3 groups. Patients in group A solely received ¹³¹I treatment; group B1 underwent a methylprednisolone treatment in combination with ¹³¹I treatment; and group B2 received an RTX in combination with ¹³¹I treatment. Hyperthyroidism treatment outcomes, orbital volumetry, ophthalmic assessments, serum cytokine levels, and adverse effects were measured after treatment. Results: The orbital volumetry principle was significantly different from 24 weeks after the start of treatment among all 3 groups, and improvements in most ophthalmic parameters were regarded significantly different among 3 groups (all p < 0.05). The expression levels of miR-146a and most serum cytokines were regarded significantly different from 24 weeks after the start of treatment among 3 groups (all p < 0.05). Conclusions: In comparison with other therapies, RTX treatment in combination with ¹³¹I treatment is considered to be more effective for hyperthyroidism with active GO.

Breast cancer is a major public health concern, due to its increasing incidence and limited effective treatment. The present study aimed to investigate the expression of microRNA (miR)-194-5p and its roles in breast cancer. The expression levels of miR-194-5p and SRY-box 17 (SOX17) mRNA were detected in breast cancer tissues and cell lines by reverse transcription-quantitative polymerase chain reaction. The protein expression levels were determined by western blotting. In addition, MTT, colony formation, scratch and Transwell assays were use to evaluate the characteristics of MCF-7 cells with miR-194-5p knockdown. The target verification of miR-194-5p was determined by luciferase reporter assay. Furthermore, tumor-bearing nude mice with miR-194-5p knockdown were used to assess the effects of miR-194-5p on tumor activity. In breast cancer tissues, miR-194-5p was upregulated, whereas SOX17 was downregulated. In addition, the expression levels of SOX17 and phosphorylated (p)-β-catenin in the cytosol and nucleus were increased in the miR-194-5p inhibitor group. In addition, cell proliferation, migration and invasion were inhibited in response to miR-194-5p knockdown. The luciferase reporter assay confirmed that SOX17 was a target gene of miR-194-5p. In the mouse studies, knockdown of miR-194-5p suppressed tumor growth and promoted SOX17 expression in nude mice with breast cancer. These findings suggested that knockdown of miR-194-5p may increase the expression of SOX17 and regulate the Wnt/β-catenin signaling pathway in breast cancer cells; therefore, miR-194-5p may be considered a potential target for breast cancer prevention.

Background:Our study aims to explore the effect of total parathyroidectomy (PTX) with forearm autotransplantation (FAT) on the quality of life and recurrence of secondary hyperparathyroidism (SHPT) in chronic kidney disease patients.Methods:A total of 104 chronic kidney disease patients with SHPT were enrolled and divided into the PTX (n = 62) and PTX + FAT (n = 42) groups. The operation efficacy was evaluated by analyzing preoperative and postoperative values, including levels of intact parathyroid hormone (iPTH), serum phosphorus, serum calcium, alkaline phosphatase (ALP), calcium-phosphorus product, signs and symptoms, and MOS 36-item short-form health survey (SF-36) scores. Moreover, complications and recurrences were followed up for 12 months after the operation. Binary logistic regression was to present the risk factors for the recurrence of chronic kidney disease patients with SHPT.Results:Compared with the preoperative values, the PTX and PTX + FAT groups showed decrease postoperative levels of iPTH, serum phosphorus, serum calcium, calcium-phosphorus product, bone pain, and skin pruritus at all time periods. The PTX and PTX + FAT groups demonstrated decreased ALP, fracture or deformity, and coronary artery calcification at 1 month, decreased short stature at 3 months after the operation but increased SF-36 score after operation. Compared with the PTX group, the level of iPTH decreased and the levels of serum calcium, calcium-phosphorus product increased at 3, 6, and 12 months after the operation in the PTX + FAT group. The levels of ALP, fracture or deformity, short stature, and SF-36 decreased separately at 1 week and 6 and 12 months after the operation, along with the decrease of coronary artery calcification and the recurrence rate, respectively, at 6 and 12 months after the operation in the PTX + FAT group when compared with those in the PTX group. Logistic regression analysis evidenced that the preoperative iPTH level, SF-36 score, and operation type were the risk factors for the recurrence of chronic kidney disease with SHPT.Conclusion:Total PTX combined with FAT is more effective in improving the quality of life and reducing the recurrence of chronic kidney disease with SHPT than PTX alone.

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Background Bridge to elective surgery (BTS) using self-expanding metal stents (SEMSs) is a common alternative to emergency surgery (ES) for acute malignant left-sided colonic obstruction (AMLCO). However, studies regarding the long-term impact of BTS are limited and have reported unclear results. Methods A multicenter observational study was performed at three hospitals from April 2012 to December 2019. Propensity score matching (PSM) was introduced to minimize selection bias. The primary endpoint was overall survival. The secondary endpoints included surgical approaches, primary resection types, total stent-related adverse effects (AEs), surgical AEs, length of hospital stay, 30-day mortality and tumor recurrence. Results Forty-nine patients in both the BTS and ES groups were matched. Patients in the BTS group more often underwent laparoscopic resection [31 (63.3%) vs. 8 (16.3%), p < 0.001], were less likely to have a primary stoma [13 (26.5%) vs. 26 (53.1%), p = 0.007] and more often had perineural invasion [25 (51.0 %) vs. 13 (26.5 %), p = 0.013]. The median overall survival was significantly lower in patients with stent insertion (41 vs. 65 months, p = 0.041). The 3-year overall survival (53.0 vs. 77.2%, p = 0.039) and 5-year overall survival (30.6 vs. 55.0%, p = 0.025) were significantly less favorable in the BTS group. In multivariate Cox regression analysis, stenting (hazard ratio(HR) = 2.309(1.052–5.066), p = 0.037), surgical AEs (HR = 1.394 (1.053–1.845), p = 0.020) and pTNM stage (HR = 1.706 (1.116–2.607), p = 0.014) were positively correlated with overall survival in matched patients. Conclusions Self-expanding metal stents as “a bridge to surgery” are associated with more perineural invasion, a higher recurrence rate and worse overall survival in patients with acute malignant left-sided colonic obstruction compared with emergency surgery.

The transcription factor, forkhead box P2 (FOXP2) has tumor-suppressive effects in several types of cancer. However, the regulatory role and underlying mechanism of FOXP2 in thyroid cancer (THCA) is not completely understood. In the present study, the mRNA expression levels of FOXP2 and ribosomal protein S6 kinase A6 (RPS6KA6) were evaluated using the GEPIA database and THCA cell lines. The association between FOXP2 and RPS6KA6 was analyzed using the LinkedOmics, and GEPIA databases. Then, the binding sites of FOXP2 and the RPS6KA6 promotor was predicted using the JASPAR database, and verified using a dual-luciferase reporter assay and chromatin immunoprecipitation. In addition, functional assays investigating FOXP2 and RPS6KA6 were conducted in the TPC-1 cell line. The data showed that FOXP2 and RPS6KA6 mRNA expression levels were decreased in the THCA tissues, and cell lines. Overexpression of FOXP2 inhibited cell proliferation and promoted apoptosis in the THCA cell lines. Furthermore, RPS6KA6 mRNA expression levels were reduced in THCA and were correlated with FOXP2 expression level. Mechanistic studies revealed that FOXP2 binds directly to the promotor region of RPS6KA6 and modulated the expression level of RPS6KA6 transcriptionally. In addition, rescue experiments showed that knockdown of RPS6KA6 expression reversed the effects of FOXP2 overexpression on THCA cell proliferation and apoptosis, and the regulation of FOXP2/RPS6KA6 may be associated with the PI3K/AKT pathway. In summary, FOXP2 was associated with the proliferation and apoptosis of human THCA cells via the transcriptional activation of RPS6KA6. The FOXP2/RPS6KA6 axis could be a promising target for the treatment of THCA.

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PurposeBridge to elective surgery (BTS) using self-expanding metal stents (SEMS) is a common alternative to emergency surgery (ES) for acute malignant left-sided colonic obstruction (AMLCO). However, the study regarding long-term impact of BTS is limited and unclear.MethodsA multicenter observational study was performed at three hospitals from April 2012 to December 2019. Propensity score matching (PSM) was introduced to minimize selection bias. The primary endpoint was overall survival. The secondary endpoints included surgical approaches, primary resection types, total stent related adverse effects (AEs), surgical AEs, length of hospital stay, 30-day mortality and tumor recurrence.Results49 patients in both BTS and ES group were matched. Patients in the BTS group more often underwent laparoscopic resection (31 [63.3%] vs 8 [16.3%], p<0.001), less likely to have a primary stoma (13 [26.5%] vs 26 [53.1%], p=0.007) and more often had perineural invasion (25 [51.0%] vs 13 [26.5%], p=0.013). The median overall survival was significantly lower in patients with stent insertion (41 vs 65 months, p=0.041). 3-year overall survival (53.0% vs 77.2%, p=0.039) and 5-year overall survival (30.6% vs 55.0%, p=0.025) were significantly less favorable in the BTS group. In the multivariate Cox regression analysis, stenting (hazard ratio(HR)= 2.309(1.052-5.066), p=0.037), surgical AEs (HR=1.394(1.053-1.845), p=0.020) and pTNM stage (HR=1.706(1.116-2.607), p=0.014) were positively correlated with overall survival in matched patients. ConclusionsSelf-expanding metal stents as “a bridge to surgery” is associated with more perineural invasion, higher recurrence rate and worse overall survival in patients with acute malignant left-sided colonic obstruction compared with emergency surgery.