The lncRNA Malat1 functions as a ceRNA to contribute to berberine-mediated inhibition of HMGB1 by sponging miR-181c-5p in poststroke inflammation.

Long non-coding RNAs (lncRNAs) have been identified as essential mediators in neurological dysfunction. Our previous study shows that berberine (BBR) hampers the nuclear-to-cytosolic translocation of high-mobility group box 1 (HMGB1) in the process of poststroke inflammation. In this study, we explored the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) in the process of BBR-induced inhibition of HMGB1 in ischemic brain. Before the 60-min MCAO surgery, the mice were pretreated with BBR (50 mg· kg-1 per day, ig) for 14 days or ICV injected with specific lentiviral vector or shRNA. We showed that MCAO caused marked increase in the expression Malat1 and HMGB1 in the ipsilateral cortex, which was significantly attenuated by pretreatment with BBR. Knockdown of Malat1 attenuated the inflammatory injury after brain ischemia, whereas overexpression of Malat1 exacerbated ischemic brain inflammation. Overexpression of Malat1 also reversed BBR-induced reduction of HMGB1 and proinflammatory cytokines. The above results suggested a potential correlation between Malat1 and stroke inflammation. Based on informatics analysis we predicted that HMGB1 was a direct downstream target of miR-181c-5p, whereas Malat1 acted as a competitive endogenous RNA (ceRNA) for miR-181c-5p targeted the 3'-UTR of HMGB1 to promote inflammation after ischemic stroke. Knockdown of Malat1 significantly decreased HMGB1 level, which could be abrogated by transfection with miR-181c-5p inhibitors. Taken together, our results demonstrate for the first time that Malat1/miR-181c-5p/HMGB1 axis may be a key pathway of BBR-induced antiinflammation effects in stroke, and they may provide a novel avenue for targeted therapy.

Type 2 Cesarean Scar Pregnancy Successfully Treated via Hysteroscopy-Assisted Laparoscopy.

STUDY OBJECTIVE: To evaluate the efficacy of hysteroscopy-assisted laparoscopy as a treatment strategy for type 2 cesarean scar pregnancy at gestational age >8 weeks. DESIGN: Retrospective case series (Canadian Task Force classification II-3). SETTING: A tertiary hospital. PATIENTS: Eight women with type 2 cesarean scar pregnancy at a gestational age >8 weeks. INTERVENTIONS: All patients underwent hysteroscopy-assisted laparoscopic resection and isthmus repair of cesarean scar pregnancy. MEASUREMENTS AND MAIN RESULTS: All patients underwent removal of the cesarean scar pregnancy and complete repair of the uterine scar defect. The median operative time was 123.0 minutes (range, 100-168 minutes), median blood loss was 65.0 mL (range, 20-100 mL), and median length of hospital stay was 9.1 days (range, 8-12 days). There were no adverse reactions. The mean time to serum ß-human chorionic gonadotropin (ß-HCG) resolution was 22.9 days (range, 14-30 days), and menstruation resumed after 9 to 15 days with serum ß-HCG returning to nondetectable levels. There was no recurrence of cesarean scar pregnancy at long-term follow-up. CONCLUSION: Hysteroscopy-assisted laparoscopy may be an effective treatment for patients with type 2 cesarean scar pregnancy at gestational age >8 weeks.

Combined overexpression of cadherin 6, cadherin 11 and cluster of differentiation 44 is associated with lymph node metastasis and poor prognosis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a highly invasive lesion that frequently metastasizes to the cervical lymph nodes and is associated with a poor prognosis. Several adhesion factors, including cadherin 6 (CDH6), cadherin 11 (CDH11) and cluster of differentiation 44 (CD44), have been reported to be involved in the invasion and metastasis of multiple types of cancer. Therefore, the aim of the present study was to determine the expression of CDH6, CDH11 and CD44 in tumor tissues from patients with OSCC, and whether this was associated with the metastasis and survival of OSCC. The mRNA expression of the human tumor metastasis-related cytokines was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in OSCC tumors with or without lymph node metastasis (n=10/group). The expression of CDH6, CDH11 and CD44 in 101 OSCC and 10 normal oral mucosa samples was examined by immunohistochemical staining. The association between overall and disease-specific survival times of patients with OSCC and the expression of these three proteins was evaluated using Kaplan-Meier curves and the log-rank test. RT-qPCR results indicated that the mRNA expression of CDH6, CDH11 and CD44 was increased in OSCC patients with lymph node metastasis (2.93-, 2.01- and 1.92-fold; P<0.05). Overexpression of CDH6, CDH11 and CD44 was observed in 31/35 (89%), 25/35 (71%) and 31/35 (89%) patients, respectively. The number of OSCC patients with lymph node metastasis exhibiting CDH6, CDH11 and CD44 overexpression was significantly higher than the number of patients without lymph node metastasis exhibiting overexpression of these proteins (P=0.017, P=0.038 and P=0.007, respectively). OSCC patients with high co-expression of CDH6, CDH11 and CD44 exhibited lower disease-specific survival times (P=0.047; χ2=3.933) when compared with OSCC patients with low co-expression of these adhesion factors. CDH6, CDH11 and CD44 serve important roles in OSCC metastasis and the combined use of these factors as biomarkers may improve the accuracy of the prediction of cancer metastases and prognosis.

[Inhibitory Effect of Histone Deacetylase Inhibitor SAHA on Proliferation of Mouse Multiple Myeloma Cell Line SP2/0 in vitro and in vivo].

OBJECTIVE: To explore the anti-myeloma effect of suberoylanilide hydroxamic acid (SAHA) and on mouse myeloma cell line SP2/0 in vitro and in vivo and its mechanism. METHODS: The inhibitory effect of SAHA on SP2/0 cells was measured by CCK-8 assay,and the apoptosis and cell cycle were analyzed by flow cytometry FACS. The protein expression of Caspase-3 and p53 of SP2/0 cells treated with SAHA were examined by Western blot. Annexin V/7-AAD double staining was performed to detect the apoptosis of SP2/0 induced by SAHA in vitro. SP2/0 cells (1×106) resuspended in 200 µl PBS were inoculated subcutaneously and intravenously into BALB/c mice, so as to establish aggressive or non-aggressive myeloma-bearing mouse models respectively. On day 3 after modeling, mice received SAHA or vehicle control treatment by intraperitoneal injection. The dose of SAHA was 60 mg/kg·d, 5 times a week for 3 weeks. RESULTS: In SAHA-treated SP2/0 cells, the proliferation inhibition rate and apoptotic cells increased in a dose dependent manner. Also, SAHA significantly increased the ratio of cells in G2 phase and decreased in S phase. Molecular mechanisms of apoptosis and cell cycle arrest of SP2/0 induced by SAHA partly correlated with up-regulating the expression level of Caspase-3 and p53. In the non-aggressive myeloma-bearing mice, SP2/0 cells disappeared in peripheral blood after SAHA treatment. In the aggressive myeloma-bearing mice, inhibition of tumor growth and prolongation of the cell survival were observed after SAHA treatment. CONCLUSION: SAHA inhibited SP2/0 cell proliferation, this effect associates with inducing apoptosis and cell cycle arrest, the mechanism of SAHA ralates partly with activating Caspase-3 and p53 pathway.

Evaluation of the Efficacy of Ultrasound-Guided Local Lauromacrogol Injection Combined with Aspiration for Cesarean Scar Pregnancy: A Novel Treatment.

OBJECTIVES: To evaluate the efficacy of ultrasound-guided local lauromacrogol injection combined with aspiration for treating cesarean scar pregnancy (CSP). METHODS: From July 2016 to December 2016, 18 patients diagnosed with CSP were treated with ultrasound-guided local lauromacrogol injection combined with aspiration. Clinical data and outcome were analysed. RESULTS: All patients were treated successfully. The amount of bleeding ranged between 10 and 50 mL. The duration of hospitalization ranged between 2 and 11 days. Serum ß-human chorionic gonadotropin (ß-hCG) decreased to the nondetectable level within 19-41 days. Menstruation recovery occurred after 10-24 days of normalization of serum ß-hCG level. Reproductive functions were preserved, and there were no untoward effects or complications. CONCLUSIONS: Ultrasound-guided local lauromacrogol injection combined with aspiration is an effective CSP therapy, as it was associated with a high success rate, short hospitalization and fast recovery. However, its wider application and popularization have to be validated on a larger patient population affected by CSP.