Cervical carcinoma progression is aggravated by lncRNA ZNF281 by binding KLF15.

OBJECTIVE: This study aims to explore the biological roles of long non-coding RNA (lncRNA) ZNF281 and KLF15 in regulating cervical carcinoma progression. PATIENTS AND METHODS: Differential expressions of ZNF281 in 58 collected cervical carcinoma and normal tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between ZNF281 and clinicopathologic characteristics in cervical carcinoma patients was analyzed. By generating ZNF281 knockdown model in HeLa and SiHa cells through the transfection of shZNF281, migratory ability changes were examined via transwell and wound healing assay. The role of ZNF281 in in vivo tumorgenicity of cervical carcinoma was examined by implanting xenografted cancers in nude mice. The downstream target of ZNF281 and their interaction were assessed by bioinformatics tool and Dual-Luciferase reporter assay, respectively. Finally, co-regulations of ZNF281 and KLF15 on cervical carcinoma progression were elucidated. RESULTS: ZNF281 was upregulated in cervical carcinoma tissues and cell lines. It was correlated to TNM staging, and incidences of lymphatic metastasis and distant metastasis in cervical carcinoma patients, while it was unrelated to age and tumor size. The knockdown of ZNF281 effectively attenuated migratory ability in HeLa and SiHa cells. Besides, knockdown of ZNF281 also reduced tumorigenicity of cervical carcinoma in nude mice. KLF15 was the downstream gene binding ZNF281, and they were negatively correlated to each other in cervical carcinoma tissues. Notably, KLF15 was responsible for ZNF281-induced regulation on cervical carcinoma migration. CONCLUSIONS: LncRNA ZNF281 is upregulated in cervical carcinoma samples, and it is correlated to lymphatic metastasis, distant metastasis, and poor prognosis in cervical carcinoma patients. By targeting KLF15, ZNF281 triggers migratory potential in cervical carcinoma. We believed that ZNF281 is a promising biomarker for cervical carcinoma.

[Clinical study of Youngswick versus distal oblique osteotomy in the treatment of grade â ¢ and â £ hallux rigidus].

Objective: To investigate the clinical outcomes and effects of distal oblique osteotomy and the Youngswick osteotomy in the treatment of grade Ⅲ and Ⅳ hallux rigidus. Methods: Totally 29 patients (33 feet) suffered from grade Ⅲ and Ⅳ hallux rigidus who received the distal first metatarsal osteotomy in Ningbo NO.6 Hospital from May 2013 to December 2018 were analyzed retrospectively. Among them, there were 10 males and 19 females. The average age was (56±6) years. Seventeen cases (18 feet) underwent distal oblique osteotomy of the first metatarsal, 12 cases (15 feet) underwent the Youngswick osteotomy. The overall clinical evaluations were investigated before the operation and at the final follow-up, included the visual analogue scale (VAS) of the pain, American Orthopedic Foot & Ankle Society (AOFAS) scores, the motionrange of the first metatarsophalangeal joint and the first metatarsophalangeal joint space. The data before and after operation were compared by paired t test and non-parametric rank sum test. Results: The operation time were (1.1±0.2) hours and (1.3±0.1) hours, and the intraoperative bleeding was 35 (25, 36) ml and 35 (30, 40) ml in the distal oblique osteotomy and Youngswick osteotomy respectively. All patients were followed up for 12 to 46 months. No nonunion or delayed union occurred in all patients. All patients did not need to be operated again, and no complications such as transferring metatarsalgia, infection and osteonecrosis occurred. In the two groups, the pain VAS score decreased significantly (Z=-3.8, -3.5, both P<0.01), the first metatarsophalangeal joint dorsal extension activity increased (Z=-3.7, -3.4, both P<0.01), the AOFAS score increased (t=28.0, 15.4, both P<0.05) and the first metatarsophalangeal joint space also improved significantly (t=17.7, 14.6, P<0.05) after the operation. There was no significant difference in VAS score, the first metatarsophalangeal joint activity and Horton index between the two groups(Z=-1.3, -0.3, -0.4, all P>0.05), and there was no statistical difference inAOFAS score (t=0.1, P>0.05). But compared with it in the first distal oblique metatarsal osteotomy, the joint space with the Youngswick osteotomy after the operation was larger ((2.4±0.3) mm vs (2.1±0.4) mm, t=2.2, P=0.04). Conclusions: The oblique metatarsal osteotomy and Youngswick osteotomy can effectively relieve the pain of the hallux rigidus, increase the dorsal extension activity and joint space of the first metatarsophalangeal joint, sink the first metatarsal head, and improve the living conditions of the patients. The results of the distal metatarsal osteotomy and the Youngswick osteotomy in the treatment of stage Ⅲ and Ⅳ patients with rigid are similar, which can delay the progress of the disease.

Decoding collective communications using information theory tools.

Organisms have evolved sensory mechanisms to extract pertinent information from their environment, enabling them to assess their situation and act accordingly. For social organisms travelling in groups, like the fish in a school or the birds in a flock, sharing information can further improve their situational awareness and reaction times. Data on the benefits and costs of social coordination, however, have largely allowed our understanding of why collective behaviours have evolved to outpace our mechanistic knowledge of how they arise. Recent studies have begun to correct this imbalance through fine-scale analyses of group movement data. One approach that has received renewed attention is the use of information theoretic (IT) tools like mutual information, transfer entropy and causation entropy, which can help identify causal interactions in the type of complex, dynamical patterns often on display when organisms act collectively. Yet, there is a communications gap between studies focused on the ecological constraints and solutions of collective action with those demonstrating the promise of IT tools in this arena. We attempt to bridge this divide through a series of ecologically motivated examples designed to illustrate the benefits and challenges of using IT tools to extract deeper insights into the interaction patterns governing group-level dynamics. We summarize some of the approaches taken thus far to circumvent existing challenges in this area and we conclude with an optimistic, yet cautionary perspective.

Cytological mechanism of astragaloside IV in promoting repair of bone defects.

To explore the possible cytological mechanism underlying the role of Astragaloside IV in promoting the repair of bone defects, osteoblasts were cultured in vitro and identified using inverted phase contrast microscopy, alkaline phosphatase (ALP) staining and alizarin red staining.

Gradual onset and recovery of the Younger Dryas abrupt climate event in the tropics.

Proxy records of temperature from the Atlantic clearly show that the Younger Dryas was an abrupt climate change event during the last deglaciation, but records of hydroclimate are underutilized in defining the event. Here we combine a new hydroclimate record from Palawan, Philippines, in the tropical Pacific, with previously published records to highlight a difference between hydroclimate and temperature responses to the Younger Dryas. Although the onset and termination are synchronous across the records, tropical hydroclimate changes are more gradual (>100 years) than the abrupt (10-100 years) temperature changes in the northern Atlantic Ocean. The abrupt recovery of Greenland temperatures likely reflects changes in regional sea ice extent. Proxy data and transient climate model simulations support the hypothesis that freshwater forced a reduction in the Atlantic meridional overturning circulation, thereby causing the Younger Dryas. However, changes in ocean overturning may not produce the same effects globally as in Greenland.

TNF alpha inhibits myogenic differentiation of C2C12 cells through NF-κB activation and impairment of IGF-1 signaling pathway.

Cachexia or muscle wasting is a common condition that occurs in many chronic diseases. The wasting conditions are characterized by increased levels of TNF-α which was also known as cachectin in the past. But how TNF-α exerts its cachetic effects remains controversial. To clarify this issue, we investigated the impact of TNF-α on C2C12 cell myogenic differentiation. Our results demonstrate that myotube formation was completely inhibited by TNF-α when added to differentiating C2C12 myoblasts. The inhibitory effect of TNF-α on differentiation was accompanied by activation of NF-κB and down regulation of myogenin and Akt. Importantly, TNF-α's effect on differentiation was abolished when IGF-1 was added to the culture. IGF-1 treatment also inhibited NF-κB reporter activity and restored Akt levels. Our data suggest that TNF-α inhibits myogenic differentiation through NF-κB activation and impairment of IGF-1 signaling pathway. The reversal of TNF-α induced inhibition of myogenesis by IGF-1 may have significant therapeutic potential.

Use of azathioprine for graft-vs-host disease is the major risk for development of secondary malignancies after haematopoietic stem cell transplantation: a nationwide population-based study.

BACKGROUND: As more patients are treated by haematopoietic stem cell transplantation (HSCT), development of secondary malignancy (SM) becomes an increasingly common issue in long-term survivors. METHODS: We conducted a nationwide population-based study of the Taiwanese population to analyse patients who received HSCT between January 1997 and December 2010. Standardised incidence ratios (SIRs) were used to compare the risk of SM in HSCT patients and the general population. Multivariate analysis was performed to identify independent predictors of SM. RESULTS: Patients receiving HSCT had a significantly greater risk of developing SM (SIR 2.00; 95% confidence interval (CI) 1.45-2.69; P<0.001). Specifically, the incidence increased for cancers of the oral cavity (SIR 14.18) and oesophagus (SIR 14.75) after allogeneic HSCT. Multivariate analysis revealed an increased SIR for cancer in patients who received the immunosuppressant azathioprine. The risk of SM also increased with greater cumulative doses of azathioprine. CONCLUSIONS: This study demonstrates an increased incidence of SM in Taiwanese patients who received allogeneic HSCT, especially for cancers of the oral cavity and oesophagus. This finding is different from results in populations of Western countries. Physicians should be cautious about azathioprine use for graft-vs-host disease after HSCT.

Neandertal roots: Cranial and chronological evidence from Sima de los Huesos.

Seventeen Middle Pleistocene crania from the Sima de los Huesos site (Atapuerca, Spain) are analyzed, including seven new specimens. This sample makes it possible to thoroughly characterize a Middle Pleistocene hominin paleodeme and to address hypotheses about the origin and evolution of the Neandertals. Using a variety of techniques, the hominin-bearing layer could be reassigned to a period around 430,000 years ago. The sample shows a consistent morphological pattern with derived Neandertal features present in the face and anterior vault, many of which are related to the masticatory apparatus. This suggests that facial modification was the first step in the evolution of the Neandertal lineage, pointing to a mosaic pattern of evolution, with different anatomical and functional modules evolving at different rates.

Bortezomib inhibits C2C12 growth by inducing cell cycle arrest and apoptosis.

Proteosome inhibitors such as bortezomib (BTZ) have been used to treat muscle wasting in animal models. However, direct effect of BTZ on skeletal muscle cells has not been reported. In the present study, our data showed that C2C12 cells exhibited a dose-dependent decrease in cell viability in response to increasing concentrations of BTZ. Consistent with the results of cell viability, Annexin V/PI analysis showed a significant increase in apoptosis after exposing the cells to BTZ for 24h. The detection of cleaved caspase-3 further confirmed apoptosis. The apoptosis induced by BTZ was associated with reduced expression of p-ERK. Cell cycle analysis revealed that C2C12 cells underwent G2/M cell cycle arrest when incubated with BTZ for 24h. Furthermore, BTZ inhibited formation of multinucleated myotubes. The inhibition of myotube formation was accompanied by decreased expression of Myogenin. Our data suggest that BTZ induces cell death and inhibits differentiation of C2C12 cells at clinically relevant doses.

Pasireotide versus octreotide in acromegaly: a head-to-head superiority study.

CONTEXT: Biochemical control reduces morbidity and increases life expectancy in patients with acromegaly. With current medical therapies, including the gold standard octreotide long-acting-release (LAR), many patients do not achieve biochemical control. OBJECTIVE: Our objective was to demonstrate the superiority of pasireotide LAR over octreotide LAR in medically naive patients with acromegaly. DESIGN AND SETTING: We conducted a prospective, randomized, double-blind study at 84 sites in 27 countries. PATIENTS: A total of 358 patients with medically naive acromegaly (GH >5 µg/L or GH nadir ≥1 µg/L after an oral glucose tolerance test (OGTT) and IGF-1 above the upper limit of normal) were enrolled. Patients either had previous pituitary surgery but no medical treatment or were de novo with a visible pituitary adenoma on magnetic resonance imaging. INTERVENTIONS: Patients received pasireotide LAR 40 mg/28 days (n = 176) or octreotide LAR 20 mg/28 days (n = 182) for 12 months. At months 3 and 7, titration to pasireotide LAR 60 mg or octreotide LAR 30 mg was permitted, but not mandatory, if GH ≥2.5µg/L and/or IGF-1 was above the upper limit of normal. MAIN OUTCOME MEASURE: The main outcome measure was the proportion of patients in each treatment arm with biochemical control (GH <2.5 µg/L and normal IGF-1) at month 12. RESULTS: Biochemical control was achieved by significantly more pasireotide LAR patients than octreotide LAR patients (31.3% vs 19.2%; P = .007; 35.8% vs 20.9% when including patients with IGF-1 below the lower normal limit). In pasireotide LAR and octreotide LAR patients, respectively, 38.6% and 23.6% (P = .002) achieved normal IGF-1, and 48.3% and 51.6% achieved GH <2.5 µg/L. 31.0% of pasireotide LAR and 22.2% of octreotide LAR patients who did not achieve biochemical control did not receive the recommended dose increase. Hyperglycemia-related adverse events were more common with pasireotide LAR (57.3% vs 21.7%). CONCLUSIONS: Pasireotide LAR demonstrated superior efficacy over octreotide LAR and is a viable new treatment option for acromegaly.

Gap opening and orbital modification of superconducting FeSe above the structural distortion.

We utilize steady-state and transient optical spectroscopies to examine the responses of nonthermal quasiparticles with respect to orbital modifications in normal-state iron-chalcogenide superconductors. The dynamics shows the emergence of gaplike quasiparticles (associated with a ~36 meV energy gap) with a coincident transfer of the optical spectral weight in the visible range, at temperatures above the structural distortion. Our observations suggest that opening of the high-temperature gap and the lattice symmetry breaking are possibly driven by short-range orbital and/or charge orders, implicating a close correlation between electronic nematicity and precursor order in iron-based superconductors.

Coronary artery dilation among patients with paediatric-onset systemic lupus erythematosus.

OBJECTIVES: This study aimed to evaluate increased coronary artery dimensions in patients with paediatric-onset systemic lupus erythematosus (SLE) in comparison with healthy controls, and to identify risk factors associated with increased coronary artery dimensions in the SLE patients. METHODS: As part of a longitudinal cohort study of coronary artery disease (CAD) in paediatric-onset SLE, 83 children with SLE and 36 healthy controls were enrolled for a cross-sectional analysis. Their coronary artery diameters were measured by echocardiography while their body mass index (BMI), blood pressure, and other cardiovascular factors were recorded. The age at diagnosis, serum uric acid (UA) and creatinine levels, and other lupus-related factors were further evaluated in SLE patients. Data were analysed using linear regression. RESULTS: Mean body surface area (BSA)-adjusted dimensions of the left coronary artery (LCA) and right coronary artery (RCA) were significantly larger in SLE patients than in controls (both p < 0.001). The age at diagnosis, BMI, and serum UA and creatinine levels were associated with LCA and RCA diameters. There were no correlations between the coronary artery diameters and blood pressure, SLE duration, SLE Disease Activity Index (SLEDAI), C-reactive protein (CRP), C3, C4, anti-double-stranded-DNA (anti-dsDNA), or lipid profile. In multivariate analysis, serum UA level, age at diagnosis, and BMI were consistently associated with coronary artery dimensions (p < 0.001, p = 0.008, and p = 0.006 for LCA; p = 0.020, 0.013, and 0.008 for RCA). CONCLUSIONS: Increased coronary artery diameters were found in children with SLE and were associated with higher serum UA levels. The pathogenic mechanisms warrant further investigation.

Current treatment of sacral giant cell tumour of bone: a review.

Sacral giant cell tumour of bone has an insidious onset and slow growth rate, making early diagnosis difficult. The tumour has a high recurrence rate and is often fatal. Magnetic resonance imaging and computed tomography (CT), including CT-guided fine-needle biopsy, are useful for early diagnosis. Although therapy for sacral giant cell tumour often involves surgical resection and reconstruction challenges, improvements in various treatment modalities, including arterial embolization and radiotherapy, have widened the effective treatment options. The current surgical and adjuvant treatment modalities available for the management of sacral giant cell tumour are systematically reviewed and a suggested treatment algorithm is provided. En bloc excision remains the surgical procedure of choice, with functional reconstruction important in cases where the lesion is high in the sacrum. The use of adjuvant radiotherapy and chemotherapy remains controversial and should be studied further. Determination of the optimum treatment for sacral giant cell tumour will require randomized controlled trials. Early diagnosis, complete surgical resection with tumour-free margins and comprehensive treatment are important for local tumour control and improved outcome.

A pterion keyhole approach for the treatment of anterior circulation aneurysms.

The supraorbital keyhole approach is most frequently used in treatment for lesions within the anterior cranial base. However, it has some drawbacks, including cosmetically poor appearance of the scar, forehead deformity, and difficulty in dealing with some kinds of middle cerebral artery (MCA) and internal carotid artery (ICA) aneurysms. Therefore, we have developed a small pterion keyhole approach for an alternative access to treat anterior circulation aneurysms. An oblique skin incision about 3-5 cm in length was made just from 1.0 cm anterior to the superficial temporal artery at the level of the zygomatic arch, curved just below the temporal line to the forehead, and stopped at the hairline over the sylvian fissure. Then a small craniotomy (2-3 cm) was made just over the sylvian fissure and the aneurysms were exposed through the lateral cerebral fissure. We used this approach to treat 40 patients with aneurysms located in posterior communicating arteries (n=14), the MCA (n=10), the anterior communicating arteries (n=9), the anterior cerebral artery (n=1), the ophthalmic arteries (n=3), and the ICA (n=3). The general outcome of all patients was good without serious complications from the surgical technique even though 3 cases underwent intraoperative premature rupture of the aneurysms. No approach-related complication occurred except that one patient had vasospasm 2 days after the aneurysm clipping. In conclusion, this pterion keyhole approach can achieve the best operative effect for the treatment of intracranial anterior circulation aneurysms in a selective group of patients with several advantages over traditional craniotomy including minor tissue damage, less brain retraction, a superior cosmetic result, and shorter duration of surgery. Moreover, the operative field becomes wider in the deep area, providing sufficient space for microscope-assisted surgery without the need for highly specialized instruments.

Minimally invasive keyhole approach for removal of a migratory balloon complicated by endovascular embolization of a carotid-cavernous fistula.

PURPOSE: This report presents our experience in using a minimally invasive keyhole approach to remove a migratory balloon in the cerebral artery in one patient. CASE REPORT: A 19-year-old male suffered from carotid-cavernous fistula after craniofacial trauma two months previously. The patient received endovascular embolization of a carotid-cavernous fistula with detachable balloons. Unfortunately, migration of one balloon to the right middle cerebral artery (MCA) at the M1-M2 junction was noted after detaching the balloon during this procedure. Volume expansion, anticoagulation therapy and an emergency pterional keyhole approach with removal of the displaced balloon were performed successfully. Transient left hemiparesis due to temporary occlusion of the right middle cerebral artery by the balloon was promptly alleviated. There was no definite neurological sequel after the operation. CONCLUSIONS: Although detachable balloon embolization is the best initial treatment of direct carotid-cavernous fistulas, it is likely to migrate to downstream cerebral arteries. We recommend a minimally invasive pterional keyhole approach as a good alternative for treating such endovascular complications to improve outcome.

Minimally invasive approaches to treat simultaneous occurrence of glioblastoma multiforme and intracranial aneurysm -- case report.

Primary brain tumors associated with intracranial aneurysm are rare. A combination of glioblastoma multiforme (GBM) with cerebral aneurysm is even more rare. We present a 67-year-old female, who suffered from progressive weakness of the right limbs and dysphasia for 2 days. She was referred from another hospital with impression of having a brain tumor. The non-enhanced computed tomographic (CT) scan of the brain showed a mass lesion over the left parietal region, and another tiny lesion with relatively high density over the left suprasellar region. After admission, the carotid angiogram revealed a 13 x 12 x 14 mm aneurysm with a base about 8 mm from the anterior wall of the left supraclinoid internal carotid artery (ICA) between the left ophthalmic artery and the left anterior choroid artery. We first clipped the aneurysm by a basal pterion keyhole approach. One week later, the tumor was en bloc removed by a small left parietal craniotomy under the guidance of a navigator. The final diagnosis was confirmed by histopathological examination as GBM. After the surgeries, the patient received palliative radiotherapy with a dose of 4000 cGy. She recovered well with no evidence of recurrence of the tumor one year after the operations. In this report, the careful diagnosis and the possible mechanisms of concurring GBM and cerebral aneurysm, as well as the strategies of surgical treatment involving minimally invasive approaches are discussed.

A high-resolution absolute-dated late Pleistocene Monsoon record from Hulu Cave, China.

Oxygen isotope records of five stalagmites from Hulu Cave near Nanjing bear a remarkable resemblance to oxygen isotope records from Greenland ice cores, suggesting that East Asian Monsoon intensity changed in concert with Greenland temperature between 11,000 and 75,000 years before the present (yr. B.P.). Between 11,000 and 30,000 yr. B.P., the timing of changes in the monsoon, as established with 230Th dates, generally agrees with the timing of temperature changes from the Greenland Ice Sheet Project Two (GISP2) core, which supports GISP2's chronology in this interval. Our record links North Atlantic climate with the meridional transport of heat and moisture from the warmest part of the ocean where the summer East Asian Monsoon originates.