circular RNA circ-231 promotes protein biogenesis of TPI1 and PRDX6 through mediating the interaction of eIF4A3 with STAU1 to facilitate unwinding of secondary structure in 5' UTR, enhancing progression of human esophageal squamous cell carcinoma (ESCC).

Background: The nuclear cap-binding complex (CBC)-dependent translation (CT) is an important initial translation pathway for 5'-cap-dependent translation in normal mammal cells. Eukaryotic translation initiation factor 4A-III (eIF4A3), as an RNA helicase, is recruited to CT complex and enhances CT efficiency through participating in unwinding of secondary structure in the 5' UTR. However, the detailed mechanism for eIF4A3 implicated in unwinding of secondary structure in the 5' UTR in normal mammal cells is still unclear. Specially, we need to investigate whether the kind of mechanism in normal mammal cells extrapolates to cancer cells, e.g. ESCC, and further interrogate whether and how the mechanism triggers malignant phenotype of ESCC, which are important for identifying a potential therapeutic target for patients with ESCC. Methods: Bioinformatics analysis, RNA immunoprecipitation and RNA pulldown assays were performed to detect the interaction of circular RNA circ-231 with eIF4A3. In vitro and in vivo assays were performed to detect biological roles of circ-231 in ESCC. RNA immunoprecipitation, RNA pulldown, mass spectrometry analysis and co-immunoprecipitation assays were used to measure the interaction of circ-231, eIF4A3 and STAU1 in HEK293T and ESCC. In vitro EGFP reporter and 5' UTR of mRNA pulldown assays were performed to probe for the binding of circ-231, eIF4A3 and STAU1 to secondary structure of 5' UTR. Results: RNA immunoprecipitation assays showed that circ-231 interacted with eIF4A3 in HEK293T and ESCC. Further study confirmed that circ-231 orchestrated with eIF4A3 to control protein expression of TPI1 and PRDX6, but not for mRNA transcripts. The in-depth mechanism study uncovered that both circ-231 and eIF4A3 were involved in unwinding of secondary structure in 5' UTR of TPI1 and PRDX6. More importantly, circ-231 promoted the interaction between eIF4A3 and STAU1. Intriguingly, both circ-231 and eIF4A3 were dependent on STAU1 binding to secondary structure in 5' UTR. Biological function assays revealed that circ-231 promoted the migration and proliferation of ESCC via TPI1 and PRDX6. In ESCC, the up-regulated expression of circ-231 was observed and patients with ESCC characterized by higher expression of circ-231 have concurrent lymph node metastasis, compared with control. Conclusions: Our data unravels the detailed mechanism by which STAU1 binds to secondary structure in 5' UTR of mRNAs and recruits eIF4A3 through interacting with circ-231 and thereby eIF4A3 is implicated in unwinding of secondary structure, which is common to HEK293T and ESCC. However, importantly, our data reveals that circ-231 promotes migration and proliferation of ESCC and the up-regulated circ-231 greatly correlates with tumor lymph node metastasis, insinuating that circ-231 could be a therapeutic target and an indicator of risk of lymph node metastasis for patients with ESCC.

A high acromion-greater tuberosity impingement index increases the risk of retear after arthroscopic rotator cuff repair.

BACKGROUND: No evaluation has been done on the relationship of the acromion-greater tuberosity impingement index (ATI) with retear after arthroscopic rotator cuff repair (ARCR). Our purpose was to evaluate whether a higher ATI is associated with retear after ARCR. METHODS: 132 patients received ARCR and underwent MRI scan at a one year follow-up to assess tendon healing, and the findings were graded no retear (NR), partial-thickness retear (PR) or full-thickness retear (FR). The ATI, the critical shoulder angle (CSA), acromion index (AI) and lateral acromial angle (LAA) were measured with postoperative radiographs. Functional scores were obtained preoperatively and at a one year follow-up. RESULTS: Postoperative Constant scores and ASES scores were significantly different between groups with inferior outcomes in the FR group (p < 0.05 for all). The UCLA score was significantly better in the NR group compared with the PR and FR groups (p < 0.05), and in the PR group compared with the FR group (p < 0.05). For ATI and CSA, the values of the PR and FR groups were larger than the NR group (p < 0.05 for all), but there were no significant differences between the PR and FR groups (p > 0.05 for all). No significant differences were observed with regard to the AI and LAA (p > 0.05, respectively). The repair integrity was positively related to the ATI (0.304, p < 0.05) and CSA (0.252, p < 0.05), but not related to the AI or LAA (p > 0.05 for both). ATI was not related to any functional scores (p > 0.05 for all). CONCLUSION: This study revealed that the ATI was positively related to rotator cuff retear. Patients with retears had significantly greater ATIs after ARCR. Level of Evidence: III, case-control study.

linc01305 promotes metastasis and proliferation of esophageal squamous cell carcinoma through interacting with IGF2BP2 and IGF2BP3 to stabilize HTR3A mRNA.

Evidence shows that long noncoding RNAs (lncRNAs) modulate mRNAs of multiple genes by post-transcriptional regulation. However, in esophageal squamous cell carcinoma, lncRNAs involvement in post-transcriptional regulation of mRNAs have been rarely reported. In this study, we investigated a novel mechanism of linc01305 promoting metastasis and proliferation of ESCC. The results for real-time quantitative reverse transcription PCR (qRT-PCR) and fluorescence in situ hybridization showed that linc01305 was highly expressed and predominantly located in cytoplasm of human esophageal cancer cells. Transwell and colony formation assays confirmed that linc01305 promoted migration and proliferation of esophageal cancer cells. RNA-seq, linc01305 pulldown, mass spectrometry, RNA immunoprecipitation and mRNA stability assays demonstrated that linc01305 stabilized mRNA of target gene HTR3A through interacting with IGF2BP2 and IGF2BP3. Taken together, our data unveils a novel mechanism in which cytoplasmic linc01305 stabilizes HTR3A mRNA through interacting with IGF2BP2 and IGF2BP3 and thereby promotes metastasis and proliferation of ESCC.

Transdermal buprenorphine patch versus oral celecoxib for pain management after total knee arthroplasty: An open- label, randomized controlled trial.

BACKGROUND: This study was performed to evaluate the analgesic efficacy and safety of transdermal buprenorphine (TDB) patched for post-operative pain control after total knee arthroplasty (TKA). The hypothesis was that patients receiving the TDB patch would have less pain in comparison to those treated with the oral COX-2 inhibitor celecoxib without increasing side effects. PATIENTS AND METHODS: A total of 160 patients scheduled for primary TKA were randomly assigned to two groups: patients provided the TDB patch (10µg/h) (TDB group) and those provided oral celecoxib (CX group). The outcomes were pain scores measured using the visual analogue scale (VAS) during rest and activity, as well as morphine requirement, operated knee functional recovery and adverse events post-operatively. RESULTS: The total morphine given during the first 72h post-operatively was significantly lower in the TDB group than CX group. The VAS scores were significantly lower in the TDB group than CX group during rest at 2, 4, 6, 12, 24 and 48h post-operatively, and during activity at 12, 24 and 48h and 3 days post-operatively. The mean range of motion on post-operative days (PD) 1, 2 and 3 were significantly greater in the TDB group. In addition, the Lysholm score was significantly higher in the TDB group on PD 3. There were no remarkable adverse events in either group. DISCUSSION: Use of the TDB patch provides effective pain relief and reduces the requirement for rescue morphine without increasing side effects in comparison with oral celecoxib during the early post-operative stage following TKA. LEVEL OF EVIDENCE: II.

Safety and efficacy of tranexamic acid with epinephrine for prevention of blood loss following surgery for trochanteric femoral fractures.

OBJECTIVE: This study aimed to determine whether the local administration of tranexamic acid (TXA) combined with diluted epinephrine (DEP) reduces blood loss and the need for transfusions compared with the administration of TXA alone following surgery for trochanteric femoral fractures. METHODS: Hundred patients were enrolled in this study. In the target group (TXA/DEP group: n=50; 19 men and 31 women, mean age 72.5±11.1 years), the surgical sites were injected with 35 mL normal saline mixed with 3 g of TXA with 0.2 mg of DEP at a 1:200,000 dilution (TXA/DEP) immediately after musculoaponeurotic closure. In the control group (TXA group: n=50; 22 men and 28 women; mean age: 70.5±12.2 years), the surgical site was injected with 35 mL normal saline containing 3 g of TXA alone. The main outcome measures were postoperative hemoglobin (Hb) levels, hematocrit, drainage volume, and total blood loss (TBL); the secondary measures included transfusion requirements and perioperative complications. RESULTS: The mean Hb levels among patients in theTXA/DEP group were significantly lower than among those in the TXA group, measured on postoperative day 1 at 101.0±14.1 g/L vs. 106.9±10.5 g/L and day 3 as 104.2±8.2 g/L vs. 108.5±9.1 g/L, respectively (p<0.05). Drainage volume from the surgical site and TBL measured on postoperative day 2 were also significantly reduced in the TXA/DEP group vs. the TXA group, measured at 71.4±26.0 mL vs. 82.5±24.6 mL and 343.6±148.0 mL vs. 419.6±165.4 mL, respectively (p<0.05). Furthermore, 11 patients (22%) from the TXA group and 15 (30%) from the TXA/DEP group received blood transfusions; the mean number of transfusion events (1.2±0.4 vs. 1.9±0.7) and the amount of blood transfused (1.7±0.5 Units vs. 2.9±1.0 Units) was also markedly reduced in the TXA/DEP group (p<0.05). Two cases in the TXA/DEP group and three in the TXA group were diagnosed with deep vein thrombosis, a difference that did not reach statistical significance (p>0.05). CONCLUSION: Local administration of TXA with DEP reduced blood loss and limited the need for blood transfusions after surgery for trochanteric femoral fracture without increasing the risk of perioperative complications. Our study indicates that the local administration of TXA/DEP is safe and more effective than the administration of TXA alone in treating trochanteric femoral fractures. LEVEL OF EVIDENCE: Level III, Therapeutic study.