SP1-induced lncRNA DUBR promotes stemness and oxaliplatin resistance of hepatocellular carcinoma via E2F1-CIP2A feedback.

Oxaliplatin-based chemotherapy is widely used to treat advanced hepatocellular carcinoma (HCC), but many patients develop drug resistance that leads to tumor recurrence. Cancer stem cells (CSCs) are known to contribute to chemoresistance, the underlying mechanism, however, remains largely unknown. In this study, we discovered a specificity protein 1 (SP1)-induced long noncoding RNA--DPPA2 upstream binding RNA (DUBR) and its high expression in HCC tissues and liver CSCs. DUBR was associated with HCC progression and poor chemotherapy response. Moreover, DUBR facilitated the stemness and oxaliplatin resistance of HCC in vitro and in vivo. Mechanistically, DUBR upregulated cancerous inhibitor of protein phosphatase 2A (CIP2A) expression through E2F1-mediated transcription regulation. DUBR also exerted function by binding microRNA (miR)-520d-5p as a competing endogenous RNA to upregulate CIP2A at mRNA level. CIP2A, in turn, stabilized E2F1 protein and activated the Notch1 signaling pathway, thereby increasing the stemness feature of HCC and leading to chemoresistance. In conclusion, we identified SP1/DUBR/E2F1-CIP2A as a critical axis to activate the Notch1 signaling pathway and promote stemness and chemoresistance of HCC. Therefore, DUBR could be a potential target in HCC treatment.

Diminutive Incision Acromioplasty Assisted with Arthroscopy in the Treatment of Chinese Patients with Subacromial Impingement Syndrome / Acromioplastia de Incisión Diminuta Asistida con Artroscopia en el Tratamiento de Pacientes Chinos con Síndrome de Pinzamiento Subacromial

ABSTRACT Background: Many causes can lead to shoulder pain and subacromial impingement syndrome (SIS) is the most frequently recorded disorders. The aim of this study was to evaluate the clinical effects of diminutive incision acromioplasty assisted with arthroscopy for the treatment of Chinese patients with subacromial impingement syndrome. Subject and Methods: Twenty-two patients with 24-painful shoulders subacromial impingement syndrome were enrolled. All painful shoulders were in Grades II (8) and III (16) according to Neer's classification. Detailed physical examination was performed. Conventional radiography and subsequent magnetic resonance imaging (MRI) of the shoulder region of all patients were done. The University of California at Los Angeles Shoulder (UCLA) score system was used for all patients to evaluate their satisfaction after surgery. The preoperative recordings of the UCLA scores were collected and all enrolled cases including 24-painful shoulders were available for follow-up in 1, 3, 6, 12 months after surgery. Results: According to the UCLA scoring system, the symptom of all painful shoulders were improved after one year postoperatively. The average score before surgery from 15.4 points increased to 31.2 points postoperatively, showing a statistical difference (p < 0.05). Conclusions: A diminutive incision acromioplasty assisted with arthroscopy is a reliable approach to treat Chinese patients with subacromial impingement syndrome. All painful shoulders were obviously improved in one year after surgery.

ABSTRACT Antecedentes: Muchas causas pueden provocar dolor de hombro y síndrome de compresión subacromial (SIS) es el trastorno más frecuentemente registrado. El objetivo de este estudio fue evaluar la clínica. Efectos de la acromioplastia con incisión diminuta asistida con artroscopia para el tratamiento de Pacientes chinos con síndrome de pinzamiento subacromial. Sujeto y métodos: Se incluyeron veintidós pacientes con síndrome de afectación subacromial de 24-hombros dolorosos. Todos los hombros dolorosos estaban en Grados II (8) y III (16) de acuerdo con la clasificación de Neer. Se realizó examen físico detallado. Se realizaron radiografías convencionales y, posteriormente, imágenes de resonancia magnética (IRM) de la región del hombro de todos los pacientes. El sistema de puntuación de la Universidad de California en Los Angeles Shoulder (UCLA) se utilizó para que todos los pacientes evaluaran su satisfacción después de la cirugía. Los registros preoperatorios de las puntuaciones de UCLA se recopilaron y todos los casos incluidos, incluidos 24-hombros dolorosos, estaban disponibles para el seguimiento en 1, 3, 6 y 12 meses después de la cirugía. Resultados: De acuerdo con el sistema de puntuación de UCLA, el síntoma de todos los hombros dolorosos mejoró después de un año después de la operación. La puntuación promedio antes de la cirugía de 15.4 puntos aumentó a 31.2 puntos después de la operación, mostrando una diferencia estadística (p < 0.05) Conclusiones: Una acromioplastia de incisión diminuta asistida con artroscopia es un enfoque confiable para tratar a pacientes chinos con síndrome de pinzamiento subacromial. Todas las lesiones dolorosas se mejoraron obviamente en un año después de la cirugía.

Meta-analysis of the association between PADI4 -92C/G polymorphism and rheumatoid arthritis in the Chinese population

Many studies have evaluated the correlation between peptidylarginine deiminase 4 (PADI4) -92C/G polymorphism and rheumatoid arthritis (RA), but the results remain inconclusive. Therefore, we performed a meta-analysis in the Chinese population to provide comprehensive data on the association between PADI4 -92C/G polymorphism and RA. Eligible studies published before May 2016 were identified in PubMed and Chinese databases. The strengths of these associations were assessed by pooled odds ratios (OR) and 95% confidence interval (CI). Eight studies documenting a total of 1351 RA cases and 1585 controls were included in this meta-analysis. In the overall analysis, a significant association between the PADI4 -92C/G polymorphism and RA was found in the Chinese population (G vs C: OR=1.32, 95%CI=1.02-1.71; GG+CG vs CC: OR=1.75, 95%CI=1.20-2.53). The subgroup analyses stratified by geographic area(s) and source of controls revealed significant results in South China, in hospital-based studies and population-based studies. In summary, this meta-analysis suggested that PADI4 -92C/G polymorphism may be associated with the RA incidence in the Chinese population, especially for South China. Further studies conducted on other ethnic groups are required for definite conclusions.

Treatment strategies for early neurological deficits related to malpositioned pedicle screws in the lumbosacral canal: A pilot study.

OBJECTIVES: To employ a simple and fast method to evaluate those patients with neurological deficits and misplaced screws in relatively safe lumbosacral spine, and to determine if it is necessary to undertake revision surgery. METHODS: A total of 316 patients were treated by fixation of lumbar and lumbosacral transpedicle screws at our institution from January 2011 to December 2012. We designed the criteria for post-operative revision scores of pedicle screw malpositioning (PRSPSM) in the lumbosacral canal. We recommend the revision of the misplaced pedicle screw in patients with PRSPSM = 5' as early as possible. However, patients with PRSPSM < 5' need to follow the next consecutive assessment procedures. A total of 15 patients were included according to at least three-stage follow-up. RESULTS: Five patients with neurological complications (PRSPSM = 5') underwent revision surgery at an early stage. The other ten patients with PRSPSM < 5' were treated by conservative methods for seven days. At three-month follow-up, only one patient showed delayed onset of neurological complications (PRSPSM 7') while refusing revision. Seven months later, PRSPSM decreased to 3' with complete rehabilitation. CONCLUSIONS: This study highlights the significance of consecutively dynamic assessments of PRSPSMs, which are unlike previous implementations based on purely anatomical assessment or early onset of neurological deficits.and also confirms our hypothesis that patients with early neurological complications may not need revision procedures in the relatively broad margin of the lumbosacral canal.Cite this article: X-J. Lin. Treatment strategies for early neurological deficits related to malpositioned pedicle screws in the lumbosacral canal: A pilot study. Bone Joint Res 2016;5:46-51.

Microarray expression profile analysis of long noncoding RNAs in premature brain injury: A novel point of view.

Long noncoding RNAs (lncRNAs) are abundant in the central nervous system and have a key role in brain function as well as many neurological disorders. However, the regulatory function of lncRNAs in the premature brain has not been well studied. This study described the expression profile of lncRNAs in premature mice using microarray technology. 1999 differentially expressed lncRNAs and 955 differentially expressed mRNAs were identified. Gene Ontology (GO) and pathway analysis showed that these lncRNAs were involved in multiple biological processes, including the nervous system development and inflammatory response. Additionally, the lncRNA-mRNA-network and TF-gene-lncRNA-network were constructed to identify core regulatory lncRNAs and transcription factors. The sex-determining region of Y chromosome (SRY) gene may be a key transcription factor that regulates premature brain development and injury. This study for the first time represents an expression profile of differentially expressed lncRNAs in the premature brain and may provide a novel point of view into the mechanisms of premature brain injury.

Effect of hirulog-like peptide on middle cerebral artery occlusion-induced brain injury in mice.

Hirulog-like peptide (HLP) and low-molecular-weight heparin (LMWH) are thrombin inhibitor peptides. Our previous study demonstrated that HLP could reduce vascular neointimal formation or restenosis in animals undergoing balloon catheter injury in the carotid artery. However, the function of HLP during ischemic stroke is largely unknown. The present study investigated the effect of HLP on brain injury, which was induced by suture of middle cerebral artery occlusion in mice. Mice were divided into four groups, which included a sham group and three treatment groups. Ischemia was induced by transient suture insertion into the middle cerebral artery for 90 min, and mice were either treated with saline, HLP or LMWH. Infarct volume, neurologic deficits and apoptotic factors were measured following 1-14 days of ischemia. We demonstrated that HLP intravenous injection alleviated brain infarct volume and improved neurologic outcomes (p<0.05). HLP decreased levels of protease-activated receptor-1 (PAR-1), caspase-3, malondialdehyde (MDA) and Bcl-2-associated X protein (Bax), increased the activities of catalase and B cell lymphoma-2 (Bcl-2), and improved the ratio of Bcl-2/Bax compared with the control (p<0.05). This study indicates that HLP and LMWH reduced infarct volume and improved neurobehavioral outcomes induced by transient middle cerebral artery occlusion (tMCAO). In addition, HLP had a beneficial effect on the regulation of the thrombin receptor and key apoptosis regulators in the mouse brain. These results suggest that HLP may be a potential alternative therapy for arterial occlusion-induced cerebral ischemia.

Lycopene protects bone marrow mesenchymal stem cells against ischemia-induced apoptosis in vitro.

OBJECTIVE: Bone marrow mesenchymal stem cells (MSCs) have been identified to have the potential to differentiate into multiple types of cells. And the therapy based on transplantation of MSCs in some solid organs has been suggested in recent years. However, the rejection reaction often occurs in the transplantation of MSCs and could induce cell death. Ischemia has been reported to one of the main causes of MSCs death during transplantation. The primary objective of this study was to verify whether a natural antioxidant, lycopene, could protect MSCs from ischemia-induced apoptosis in vitro. MATERIALS AND METHODS: MSCs were isolated from bone marrow in mice femoral bone marrow. The effect of lycopene on MSCs during oxygen-glucose-serum deprivation was investigated. RESULTS: We found that lycopene protected MSCs from serum deprivation- and hypoxia-induced apoptosis. The reactive oxygen species (ROS) generation and inducible nitric oxide synthetase expression were also inhibited dose-dependently by lycopene. Further investigation revealed that lycopene could activate phosphoinositide-3 kinase (PI3K)/Akt. Pretreatment with PI3K/Akt inhibitors prevented the protective effect of lycopene on MSCs. CONCLUSIONS: Lycopene could protect MSCs from ischemia-induced apoptosis through reducing ROS generation; therefore, lycopene could be useful in MSC transplantation.

Radiofrequency ablation as first-line treatment for small solitary hepatocellular carcinoma: long-term results.

AIMS: To evaluate long-term results of patients with small solitary hepatocellular carcinoma (HCC) and well-preserved liver function who received radiofrequency ablation (RFA) as first-line treatment. MATERIALS AND METHODS: Between November 1999 and June 2007, 247 patients with solitary HCC ≤5 cm and liver status scored as Child-Pugh class A were enrolled. RFA was performed in 224 patients as first-line treatment; 23 patients excluded from RFA because of unfavorable tumor location or their unwillingness, and all of these patients converted to surgical resection. RESULTS: In the 224 patients treated with RFA, the overall 5-, 7-, 10-year survival rates were 59.8%, 55.2%, 33.9%, respectively, and the median of overall survival was 76.1 months. Complete ablation was achieved in 216 patients (96.4%). Major complications occurred in two patients (0.9%), with no treatment-related death or needle track seeding. Indocyanine green retention rate in 15 min (ICGR15) (P = 0.014) and prothrombin activity (P = 0.004) were associated with overall survival. A subgroup of patients with ICGR15 ≤ 10% and prothrombin activity >75% had 5-, 7-, 10-year survival rates of 67.1%, 64.2%, 57.1%, respectively, with a median survival of 87.7 months. The 10-year recurrence-free, tumor-free survival rates were 17.5%, 28.2%, respectively. Serum albumin was the only factor that significantly impacted recurrence-free and tumor-free survival (P = 0.008, 0.002, respectively). CONCLUSION: RFA is considered to be the treatment of first choice for patients with solitary HCC ≤5 cm and well-preserved liver function. Surgery can be used as second-line therapy for few patients if RFA is unfeasible.