[Efficacy of Barbed reposition pharyngoplasty combined with Han-Uvulopalatopharyngoplasty for the treatment of OSAHS patients].

Objective: To study the efficacy of Barbed reposition pharyngoplasty (BRP) combined with Han-Uvulopalatopharyngoplasty (H-UPPP) in surgical treatment of OSAHS patients. Methods: OSAHS patients admitted to our department from June 2021 to February 2022 who met the surgical enrollment criteria were divided into two groups by surgical procedure: H-UPPP operation group [Control group, 47 cases, including 42 males and 5 females, aged 18-64 (37.77±11.65)years, and H-UPPP+BRP group [Study group, 48 cases, including 45 males and 3 females, aged 23-60 (39.10±9.86) years]. The surgical efficacy 6 months after operation was retrospectively analyzed. Meanwhile, the relationship between the surgical efficacy and modified Friedman pharyngeal anatomical stages was analyzed. The postoperative pain VAS score at first 3 days and the incidence of foreign body sensation in pharynx after 6 months of operation were compared between the two groups. Statistical analysis was conducted by SPSS 23.0. Results: There were no significant differences in gender, age, BMI, Friedman pharyngeal anatomical stages, ESS score, AHI and LSpO2 between the two groups, preoperatively (P>0.05). There was significant difference between the two groups in ratio of cumulative time of oxygen saturation below 90% to total sleep time(CT90), preoperatively. Surgical efficacy of H-UPPP operation group was 48.9% (23/47), while H-UPPP+BRP operation group was 70.8% (34/48), which was statistically significant (χ2=4.74, P=0.029). H-UPPP+BRP group seemed to have a higher surgical efficacy than H-UPPP group in patients with Friedman Ⅱb (87% vs. 61.9%) and Ⅲ stage (44.4% vs. 15%), but there was no statistically significant difference (P>0.05). H-UPPP+BRP group had a higher pain VAS score in first three days (t=-3.10, P=0.003), also had higher incidence of pharyngeal foreign body sensation after 6 months of operation (χ2=4.727, P=0.030). Conclusions: In the surgical treatment of OSAHS patients, the overall efficacy of BRP combined H-UPPP surgery is higher than that of H-UPPP surgery alone. It may be more suitable for OSAHS patients with modified Friedman type Ⅱb and type Ⅲ stage.

miR-146a aggravates cognitive impairment and Alzheimer disease-like pathology by triggering oxidative stress through MAPK signaling.

INTRODUCTION: Mir-146a-5p has been widely recognized as a critical regulatory element in the immune response. However, recent studies have shown that miR-146a-5p may also be involved in the development of Alzheimer disease (AD). Regrettably, the related mechanisms are poorly understood. Here, we investigated the effects of miR-146a in mice models and SH-SY5Y cells treated with amyloid ß (Aß)1-42. METHODS: To create a model of AD, SH-SY5Y cells were treated with Aß1-42 and mice received intracerebroventricular injections of Aß1-42. Then, the transcriptional levels of miR-146a were estimated by real-time PCR. We transiently transfected the miR-146a-5p mimic/inhibitor into cells and mice to study the role of miR-146a. The role of signaling pathways including p38 and reactive oxygen species (ROS) was studied by using specific inhibitors. Aß and amyloid-beta precursor protein (APP)levels were measured by immunoblotting. Furthermore, Aß expression was analyzed by immunofluorescence and histochemical examinations. RESULTS: Aß1-42-stimulated SH-SY5Y cells displayed increased transcriptional levels of miR-146a and APP. Moreover, the p38 MAPK signaling pathway and ROS production were activated upon stimulation with a miR-146a-5p mimic. However, treatment with a miR-146a-5p inhibitor decreased the levels of APP, ROS, and p-p38 MAPK. A similar phenomenon was also observed in the animals treated with Aß1-42, in which miR-146a upregulation increased the expression of Aß, p-p38, and ROS, while the inhibition of miR-146a had the opposite effect. This suggests that miR-146a increases Aß deposition and ROS accumulation via the p-p38 signaling pathway. CONCLUSIONS: Our research demonstrates that miR-146a-5pa increases Aß deposition by triggering oxidative stress through activation of MAPK signaling.

miR-146a aggravates cognitive impairment and Alzheimer disease-like pathology by triggering oxidative stress through MAPK signalingmi / R-146a empeora el deterioro cognitivo y la patología tipo Alzheimer al promover el estrés oxidativo a través de la vía de señalización MAPK

Introduction: Mir-146a-5p has been widely recognized as a critical regulatory element in the immune response. However, recent studies have shown that miR-146a-5p may also be involved in the development of Alzheimer disease (AD). Regrettably, the related mechanisms are poorly understood. Here, we investigated the effects of miR-146a in mice models and SH-SY5Y cells treated with amyloid β (Aβ)1–42. Methods: To create a model of AD, SH-SY5Y cells were treated with Aβ1–42 and mice received intracerebroventricular injections of Aβ1–42. Then, the transcriptional levels of miR-146a were estimated by real-time PCR. We transiently transfected the miR-146a-5p mimic/inhibitor into cells and mice to study the role of miR-146a. The role of signaling pathways including p38 and reactive oxygen species (ROS) was studied by using specific inhibitors. Aβ and amyloid-beta precursor protein (APP)levels were measured by immunoblotting. Furthermore, Aβ expression was analyzed by immunofluorescence and histochemical examinations. Results: Aβ1–42-stimulated SH-SY5Y cells displayed increased transcriptional levels of miR-146a and APP. Moreover, the p38 MAPK signaling pathway and ROS production were activated upon stimulation with a miR-146a-5p mimic. However, treatment with a miR-146a-5p inhibitor decreased the levels of APP, ROS, and p-p38 MAPK. A similar phenomenon was also observed in the animals treated with Aβ1–42, in which miR-146a upregulation increased the expression of Aβ, p-p38, and ROS, while the inhibition of miR-146a had the opposite effect. This suggests that miR-146a increases Aβ deposition and ROS accumulation via the p-p38 signaling pathway. Conclusions: Our research demonstrates that miR-146a-5pa increases Aβ deposition by triggering oxidative stress through activation of MAPK signaling.(AU)

Introducción: miR-146a-5p es un elemento regulador clave en la respuesta inmune. Sin embargo, estudios recientes sugieren que miR-146a-5p también está involucrado en el desarrollo de la enfermedad de Alzheimer (EA), aunque aún no se conoce con exactitud el mecanismo por el que esto sucede. Analizamos los efectos de miR-146a en un modelo animal y en células SH-SY5Y expuestas a β-amiloide (Aβ)1-42. Métodos: Tratamos células SH-SY5Y con Aβ1-42 e inyectamos Aβ1-42 en los ventrículos cerebrales de ratones para generar un modelo celular y otro animal de EA. Estimamos los niveles transcripcionales de miR-146a mediante PCR en tiempo real. Al mismo tiempo, transfectamos temporalmente las células y los ratones con imitador/inhibidor de miR-146a-5p para evaluar el papel de miR-146a. Estudiamos el papel de algunas vías de señalización, como la de p38, y los niveles de especies reactivas de oxígeno (ERO) con inhibidores específicos. Los niveles de Aβ y de proteína precursora amiloidea (APP) se determinaron con inmunoblot. También se analizó la expresión de Aβ mediante inmunofluorescencia y análisis histoquímico. Resultados: Las células SH-SY5Y expuestas a Aβ1-42 mostraron altos niveles transcripcionales de miR-146a y APP. La vía de señalización p-38 MAPK y la producción de EROs se activaron al utilizar un imitador de miR-146a-5p. Sin embargo, el bloqueo de miR-146a-5p con un inhibidor redujo los niveles de APP, EROs y p-p38 MAPK. Se observó un fenómeno similar en los ratones tratados con Aβ1-42: la sobrerregulación de miR-146a aumentó la expresión de Aβ, p-p38 y EROs, mientras que la inhibición de miR-146a tuvo el efecto contrario. Esto sugiere que miR-146a está involucrado en el aumento de acumulación de Aβ y de producción de EROs por medio de la vía de señalización p-p38. Conclusiones: Nuestro estudio muestra que miR146a-5p aumenta la acumulación de Aβ al promover el estrés oxidativo a través de la activación de la vía de señalización MAPK.(AU)

[Rare tumor of internal auditory canal].

Objective: To explore the clinical features and treatment strategy of rare tumor in the internal auditory canal(IAC). Methods: A retrospective study was carried out in 213 patients with lesion of ICA form January 2010 to December 2020. According to imaging features, surgical findings, and pathological diagnosis, there were 7 cases of non-sporadic acoustic neuroma, including 2 cases of cavernous hemangioma, 2 cases of aneurysm, 1 case of intralabyrinthical schwannoma, 1 case of meningioma, and 1 case of unilateral neurofibromatosis type 2 (NF2). The clinical manifestations, imaging data and intraoperative conditions as well as the formulation of individualized treatment strategies and prognosis were comprehensively analyzed. Results: In addition to hearing loss, cavernous hemangioma early appeared damage of facial nerve. CT showed expansion and calcification of IAC. Patients with aneurysm appeared tinnitus and vertigo early. CT showed enlargement of ampulla shape of IAC. DSA or MRA can help confirm the diagnosis. Patients with intralabyrinthine schwannoma early appeared refractory vertigo. High resolution MRI was helpful for diagnosis. "Dural tail sign" can be seen on enhanced MRI of meningeoma. Neurofibromatosis type 2 usually presented as bilateral vestibular schwannomas,but a few patients presented only with unilateral vestibular schwannomas.. All patients underwent labyrinth approach resection except one patient with NF2 for followed-up. Their postoperative symptoms were relieved. No tumor recurrence was observed during 6-3 years of follow-up. Conclusions: The clinical and imaging manifestations of rare tumors of the internal auditory canal are different. The principle of treatment is also different. It is helpful to avoid the serious consequences caused by blind operation to confirm diagnosis before operation.

A radiomics method based on MR FS-T2WI sequence for diagnosing of autosomal dominant polycystic kidney disease progression.

OBJECTIVE: We aimed to construct/validate a radiomics method based on MR FS-T2WI sequence for the evaluation of kidney function in patients with autosomal dominant polycystic kidney disease (ADPKD). PATIENTS AND METHODS: The clinical data and MRI images of 114 patients with ADPKD were retrospectively analyzed. With a glomerular filtration rate of 60 mL/min per 1.73 m2 as the cutoff value, patients were divided into two groups, where there were 59 patients with GFR ≥60 mL/min per 1.73 m2 (including CKD1 and CKD2 phase) and 55 patients with GFR <60 mL/min per 1.73 m2 (including CKD3 phase and higher). All patients underwent the 3.0T MR scan of the kidney. Then, the kidney were delineated layer by layer based on the FS-T2WI sequence to obtain the volume of interest (VOI) for radiomics features extraction. The optimal radiomics features were selected by least absolute shrinkage and selection operator (LASSO). Three kinds of data modality including the pure clinical data, the pure image data and the clinical-image fused data were utilized to establish three types of models (clinical, image and with their combination) separately by five machine learning classifiers: k-nearest-neighbors (KNN), support vector machine (SVM), logistic regression (LR), random forests (RF) and multi-layer perception (MLP). Receiver operating characteristic (ROC) curve, areas under the curve (AUC), sensitivity, specificity and precision were employed to evaluate the model's effectiveness to diagnosis the glomerular filtration rate of patients with ADPKD based on different models. Besides, Delong test was applied to compare ROCs between models. RESULTS: 960 radiomics features were extracted from each VOIs, and clinical information included the gender and age of each patient. After feature selection, 23 and 21 features based on pure image data and clinical-image fused data were independently used to construct models for the kidney function evaluation. The clinical-image fused model (AUC=0.89) has better performance than the pure image model (p=0.046) and pure clinical model (p<0.001). Clinical-image fused model based on LR classifier showed the best diagnostic efficiency, with AUC=0.89, sensitivity=0.8867 and specificity=0.7959. CONCLUSIONS: The MR FS-T2WI radiomics analysis based on clinical-image fused model is instrumental in evaluating and predicting the kidney function of patients with polycystic kidney disease.

miR-146a aggravates cognitive impairment and Alzheimer disease-like pathology by triggering oxidative stress through MAPK signaling.

INTRODUCTION: Mir-146a-5p has been widely recognized as a critical regulatory element in the immune response. However, recent studies have shown that miR-146a-5p may also be involved in the development of Alzheimer disease (AD). Regrettably, the related mechanisms are poorly understood. Here, we investigated the effects of miR-146a in mice models and SH-SY5Y cells treated with amyloid ß (Aß)1-42. METHODS: To create a model of AD, SH-SY5Y cells were treated with Aß1-42 and mice received intracerebroventricular injections of Aß1-42. Then, the transcriptional levels of miR-146a were estimated by real-time PCR. We transiently transfected the miR-146a-5p mimic/inhibitor into cells and mice to study the role of miR-146a. The role of signaling pathways including p38 and reactive oxygen species (ROS) was studied by using specific inhibitors. Aß and amyloid-beta precursor protein (APP)levels were measured by immunoblotting. Furthermore, Aß expression was analyzed by immunofluorescence and histochemical examinations. RESULTS: Aß1-42-stimulated SH-SY5Y cells displayed increased transcriptional levels of miR-146a and APP. Moreover, the p38 MAPK signaling pathway and ROS production were activated upon stimulation with a miR-146a-5p mimic. However, treatment with a miR-146a-5p inhibitor decreased the levels of APP, ROS, and p-p38 MAPK. A similar phenomenon was also observed in the animals treated with Aß1-42, in which miR-146a upregulation increased the expression of Aß, p-p38, and ROS, while the inhibition of miR-146a had the opposite effect. This suggests that miR-146a increases Aß deposition and ROS accumulation via the p-p38 signaling pathway. CONCLUSIONS: Our research demonstrates that miR-146a-5pa increases Aß deposition by triggering oxidative stress through activation of MAPK signaling.

Age-growth relationships, temperature sensitivity and palaeoclimate-archive potential of the threatened Altiplano cactus Echinopsis atacamensis.

The tall (>4 m), charismatic and threatened columnar cacti, pasacana [Echinopsis atacamensis (Vaupel) Friedrich & G.D. Rowley)], grows on the Bolivian Altiplano and provides environmental and economic value to these extremely cold, arid and high-elevation (~4000 m) ecosystems. Yet very little is known about their growth rates, ages, demography and climate sensitivity. Using radiocarbon in spine dating time series, we quantitatively estimate the growth rate (5.8 and 8.3 cm yr-1) and age of these cacti (up to 430 years). These data and our field measurements yield a survivorship curve that suggests precipitation on the Altiplano is important for this species' recruitment. Our results also reveal a relationship between nighttime temperatures on the Altiplano and the variation in oxygen isotope values in spines (δ18O). The annual δ18O minimums from 58 years of in-series spine tissue from pasacana on the Altiplano provides at least decadal proxy records of temperature (r = 0.58; P < 0.0001), and evidence suggests that there are longer records connecting modern Altiplano temperatures to sea-surface temperatures (SSTs) in the Atlantic Ocean. While the role of Atlantic SSTs on the South American Summer Monsoon (SASM) and precipitation on the Bolivian Altiplano is well described, the impact of SSTs on Altiplano temperatures is disputed. Understanding the modern impact of SSTs on temperature on the Altiplano is important to both understand the impact of future climate change on pasacana cactus and to understand past climate changes on the Altiplano. This is the best quantitative evidence to date of one of the oldest known cactus in the world, although there are likely many older cacti on the Altiplano, or elsewhere, that have not been sampled yet. Together with growth, isotope and age data, this information should lead to better management and conservation outcomes for this threatened species and the Altiplano ecosystem.

[Application of tracheotomy in the treatment of severe cases of COVID-19].

Objective: To discuss the the effects, indications and protective measures of tracheotomy for severe cases of coronavirus disease 2019 (COVID-19) patients. Methods: A retrospectively analysis was conducted to explore the clinical data of COVID-19 patients who received tracheotomy in February to March 2020, and descriptive statistics were used to analyze the indication of tracheotomy, particularity of intraoperative treatment and protective measures. Results: A total of 4 cases were included in this article. All patients were successfully operated. One case had postoperative incision continuous bleeding, there were not other complications and nosocomial infection among the medical staff. The patient's condition was relieved in different degrees after the operation, who remained hospitalized. Conclusion: Tracheotomy for severe cases of COVID-19 can achieve certain curative effect, but the occurrence of tracheotomy related complications and nosocomial infection should be effectively controlled, and the risk benefit ratio of tracheotomy should be carefully weighed before surgery.

[Application of tracheotomy in the treatment of severe cases of COVID-19].

Objective: Todiscuss the the effects, indications and protective measures of tracheotomy for severe cases of 2019 novel corona virus disease(COVID-19)patients. Methods: A retrospectively analyze was conducted to explore the clinical data of ofCOVID-19 patients who received tracheotomy in February to March 2020,descriptive statistics were used to analyze the indication of tracheotomy, particularity of intraoperative treatment and protective measures. Results: A total of 4 cases were included in this article, 3 cases were successfully operated, 1 case of postoperative incision continuous bleeding, there were not other complications and nosocomial infection among the medical staff.the patient's condition was relieved in different degrees after the operation, who remain hospitalized. Conclusion: Tracheotomy for severe cases of COVID-19 can achieve certain curative effect, but the occurrence of tracheotomy related complicationsand nosocomial infection should be effectively controlled, and the risk benefit ratio of tracheotomy should be carefully weighed before surgery.

Temperature-sensitive pathways may be involved in duck embryonic developmental recovery from blastoderm dormancy during hatching.

1. Birds' newly oviposited blastoderms can survive several weeks in a dormant state during low-temperature storage. Previous studies demonstrated that there is a critical temperature range from 19 to 27°C for chicken embryos. Within this range, the embryo will diapause in a dormant state; once the temperature rises above this range, the blastoderm will break dormancy. 2. Clarifying the mechanism that initiates duck embryo developmental recovery from blastoderm dormancy will be helpful to change temperature control to improve hatching in poultry production. It was hypothesised that there might be some temperature-sensitive genes involved in initiating duck embryo developmental recovery from blastoderm dormancy. 3. To test this hypothesis, the transcriptome of the newly oviposited duck blastoderm and duck embryo (incubated for 48 hours) were sequenced to screen for differentially expressed genes with functions that had been predicted by bioinformatics. 4. The results showed that there were 2416 differentially expressed genes between the two groups, 53 of which were involved in temperature-sensitive pathways. The protein-protein interaction network combined these 53 temperature-sensitive genes and another group of 65 genes, which enriched the development pathway. These results suggested that temperature-sensitive genes may be involved in growth and development related pathways.

Preindustrial 14CH4 indicates greater anthropogenic fossil CH4 emissions.

Atmospheric methane (CH4) is a potent greenhouse gas, and its mole fraction has more than doubled since the preindustrial era1. Fossil fuel extraction and use are among the largest anthropogenic sources of CH4 emissions, but the precise magnitude of these contributions is a subject of debate2,3. Carbon-14 in CH4 (14CH4) can be used to distinguish between fossil (14C-free) CH4 emissions and contemporaneous biogenic sources; however, poorly constrained direct 14CH4 emissions from nuclear reactors have complicated this approach since the middle of the 20th century4,5. Moreover, the partitioning of total fossil CH4 emissions (presently 172 to 195 teragrams CH4 per year)2,3 between anthropogenic and natural geological sources (such as seeps and mud volcanoes) is under debate; emission inventories suggest that the latter account for about 40 to 60 teragrams CH4 per year6,7. Geological emissions were less than 15.4 teragrams CH4 per year at the end of the Pleistocene, about 11,600 years ago8, but that period is an imperfect analogue for present-day emissions owing to the large terrestrial ice sheet cover, lower sea level and extensive permafrost. Here we use preindustrial-era ice core 14CH4 measurements to show that natural geological CH4 emissions to the atmosphere were about 1.6 teragrams CH4 per year, with a maximum of 5.4 teragrams CH4 per year (95 per cent confidence limit)-an order of magnitude lower than the currently used estimates. This result indicates that anthropogenic fossil CH4 emissions are underestimated by about 38 to 58 teragrams CH4 per year, or about 25 to 40 per cent of recent estimates. Our record highlights the human impact on the atmosphere and climate, provides a firm target for inventories of the global CH4 budget, and will help to inform strategies for targeted emission reductions9,10.

Old carbon reservoirs were not important in the deglacial methane budget.

Permafrost and methane hydrates are large, climate-sensitive old carbon reservoirs that have the potential to emit large quantities of methane, a potent greenhouse gas, as the Earth continues to warm. We present ice core isotopic measurements of methane (Δ14C, δ13C, and δD) from the last deglaciation, which is a partial analog for modern warming. Our results show that methane emissions from old carbon reservoirs in response to deglacial warming were small (<19 teragrams of methane per year, 95% confidence interval) and argue against similar methane emissions in response to future warming. Our results also indicate that methane emissions from biomass burning in the pre-Industrial Holocene were 22 to 56 teragrams of methane per year (95% confidence interval), which is comparable to today.

CNDP2 Acts as an Activator for Human Ovarian Cancer Growth and Metastasis via the PI3K/AKT Pathway.

INTRODUCTION: The mechanism of tumorigenesis and metastasis of ovarian cancer has not yet been elucidated. This study aimed to investigate the role and molecular mechanism of cytosolic nonspecific dipeptidase 2 in tumorigenesis and metastasis. METHODS: Cytosolic nonspecific dipeptidase 2 expression in human ovarian cancer tissues and cell lines was assessed with methyl thiazolyl tetrazolium (MTT), clone formation, and transwell assays performed to evaluate the ability of ovarian cancer cells to proliferate and migrate. Nude mice tumor formation experiments were also performed by subcutaneously injecting cells with stable cytosolic nonspecific dipeptidase 2 knockdown and control SKOV3 cells into BALB/c female nude mice to detect changes in PI3K/AKT pathway-related proteins by Western blotting. RESULTS: Cytosolic nonspecific dipeptidase 2 was highly expressed in human ovarian cancer tissues, with its expression associated with pathological data, including ovarian cancer metastasis. A cytosolic nonspecific dipeptidase 2 stable knockdown or ectopic expression ovarian cancer cell model was established and demonstrated that cytosolic nonspecific dipeptidase 2 could promote the proliferation of ovarian cancer cells. Transwell cell migration and invasion assays confirmed that cytosolic nonspecific dipeptidase 2 enhanced cell metastasis in ovarian cancer. Furthermore, in vivo xenograft experiments demonstrated that cytosolic nonspecific dipeptidase 2 can promote the development and progression of ovarian cancer, increasing the expression of phosphorylated PI3K and AKT. CONCLUSIONS: Cytosolic nonspecific dipeptidase 2 promotes the occurrence and development of ovarian cancer through the PI3K/AKT signaling pathway.

[The inhibition effects of apatinib on cell proliferation, migration and apoptosis in esophageal carcinoma via Ras/Raf/MEK/ERK and JAK2/STAT3 pathways].

Objective: To investigate the in vitro and in vivo effects of apatinib in esophageal squamous cell carcinoma and the underlying mechanisms. Methods: The esophageal cancer cells, KYSE-150 and ECA-109, were divided into control group and apatinib treatment group at the concentrations of 2.5, 5, 10, 20 and 40 µmol/L respectively. All of experiments were performed in triplicate. MTT and colony formation assays were used to measure cell proliferation. Transwell assay was used to determine the migration capacity. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression of VEGF and VEGFR-2 was measured by real-time quantitative PCR (qRT-PCR). The concentration of VEGF in the cell supernatant was assessed by enzyme-linked immunosorbent assay (ELISA). The expression levels of MEK, ERK, p-MEK, p-ERK, JAK2, STAT3 and p-STAT3 after VEGF stimulation were detected by Western blot. Furthermore, the nude mice xenograft model was established. The tumor-bearing mice were randomly divided into control group, apatinib low dose treatment group (250 mg) and apatinib high dose treatment group (500 mg), respectively. Tumor inhibition rates of different groups were calculated. And then the expressions of VEGF and VEGFR2 were detected in xenograft tissues by immunohistochemical staining. Results: In the presence of 20 µmol/L and 40 µmol/L of apatinib for 24 hours, the migration cell numbers of KYSE-150 and ECA-109 were 428.67±4.16 and 286.67±1.53 as well as 1 123.67±70.00 and 477.33±26.84, respectively, that were significantly lower than control group (P<0.05 for all). In addition, after treatment with 10 µmol/L, 20 µmol/L and 40 µmol/L of apatinib for 7 days on KYSE-150 and ECA-109, the colony formation rates were (65.12±25.48)%, (58.19±24.73)% and (29.10±22.40)% as well as (70.61±15.14)%, (61.12±17.21)% and (43.09±11.13)%, respectively. The colony formation rates of 20 µmol/L and 40 µmol/L of apatinib treatment groups were significantly lower than control group (100.00±0.00, P<0.05). The cell cycle ratio of G(2)/M phase and apoptosis rate of control group and 20 µmol/L apatinib group in KYSE-150 cells were (12.14±2.13)% and (3.49±0.74)% as well as (26.27±3.30)% and (15.65±1.54)%, respectively. The corresponding ratios in ECA-109 cells were (3.44±0.57)% and (6.31±1.43)% as well as (22.64±2.36)% and (49.26±1.62)%, respectively. The results show that apatinib suppressed cell cycle progression at G(2)/M phase and induced cell apoptosis in both KYSE-150 and ECA-109 cells (P<0.05 for all). In the presence of 20 µmol/L and 40 µmol/L of apatinib in KYSE-150 cells, the relative levels of VEGF mRNA were (42.57±10.43)% and (25.69±1.24)%, and those of VEGF-2 mRNA were (36.09±10.82)% and (13.99±6.54)%, which were all significantly decreased compared to control group (100.00±0.00, P<0.05 for all). For ECA-109 cells, the relative expression of VEGF and VEGFR2 showed similar tendency (P<0.05 for all). Moreover, after treatment with 20 µmol/L and 40 µmol/L of apatinib in KYSE-150 cells, the VEGF concentrations were (766.48±114.27) pg/ml and (497.40±102.18)pg/ml, which were significantly decreased compared to control group [(967.41±57.75) pg/ml, P<0.05)]. The results in ECA-109 were consistent (P<0.05). Furthermore, after treatment with 40 µmol/L of apatinib in KYSE-150 and ECA-109, the relative expression of p-MEK and p-ERK were 0.49±0.05 and 0.28±0.03 as well as 0.63±0.03 and 1.22±0.15, which were significantly lower than control group (1.23±0.19 and 0.66±0.07 as well as 1.03±0.20 and 1.76±0.20; P<0.05). The relative expression of STAT3, p-STAT3 in control group and experimental group were 0.96±0.15 and 0.85±0.16 as well as 0.62±0.09 and 0.36±0.13, respectively. The results showed that the protein levels of STAT3 and p-STAT3 were significantly lower than the control group (P<0.05 for all). The inhibition rates of apatinib in xenograft nude mice were 29.25% and 19.96% for 250 mg and 500 mg treatment groups. The concentration of VEGF were (25.11±4.12) pg/ml, (16.40±2.81) pg/ml and (15.04±4.88)pg/ml for control, 250 mg and 500 mg treatment groups, respectively. Conclusions: Apatinib can inhibit cell proliferation, induce apoptosis and suppress migration of esophageal cancer cells in vitro and in vivo. This effect was mainly mediated via the alterations of Ras/Raf/MEK/ERK pathway and JAK2/STAT3 pathway.

Holocene El Niño-Southern Oscillation variability reflected in subtropical Australian precipitation.

The La Niña and El Niño phases of the El Niño-Southern Oscillation (ENSO) have major impacts on regional rainfall patterns around the globe, with substantial environmental, societal and economic implications. Long-term perspectives on ENSO behaviour, under changing background conditions, are essential to anticipating how ENSO phases may respond under future climate scenarios. Here, we derive a 7700-year, quantitative precipitation record using carbon isotope ratios from a single species of leaf preserved in lake sediments from subtropical eastern Australia. We find a generally wet (more La Niña-like) mid-Holocene that shifted towards drier and more variable climates after 3200 cal. yr BP, primarily driven by increasing frequency and strength of the El Niño phase. Climate model simulations implicate a progressive orbitally-driven weakening of the Pacific Walker Circulation as contributing to this change. At centennial scales, high rainfall characterised the Little Ice Age (~1450-1850 CE) in subtropical eastern Australia, contrasting with oceanic proxies that suggest El Niño-like conditions prevail during this period. Our data provide a new western Pacific perspective on Holocene ENSO variability and highlight the need to address ENSO reconstruction with a geographically diverse network of sites to characterise how both ENSO, and its impacts, vary in a changing climate.

miRNA-489 as a biomarker in diagnosis and treatment of cervical cancer.

miRNA-489 was shown to be a suppressor factor in many cancers, however, evidence on the effects and mechanism of miRNA-489 in progression of cervical cancer is limited. So we aimed to determine the function of miRNA-489 in cervical cancer proliferation and apoptosis in our present study. Interestingly, we found that miRNA-489 was significantly down-regulated in cervical cancer tissues. miRNA-489 overexpression inhibited the cell proliferation and improved the cell apoptosis of cervical cancer cells. Further, miRNA-489 over-expression suppressed the activation of PI3K and AKT, and stimulated P53 proteins expression. In conclusion, our results suggested that miRNA-489 may be considered as a biomarker in cervical cancer and had suppressed the cell proliferation and stimulated cell apoptosis via PI3K/AKT/P53 signaling pathway (Fig. 5, Ref. 26). Text in PDF www.elis.sk.

[The management evolution for vestibular schwannoma: history and current situation].

It has been over 200 years since the acoustic neuroma(AN) was firstly reported. From simply describing its symptoms to the decline of surgical mortality, the protection of facial and acoustic nerve function, as well as the improvement of the patients' quality of life. Physicians made efforts on evolving the diagnostic techniques and treatment strategies, and a better understanding of AN's development. The current major managements of AN are microsurgery, stereotactic radiosurgery, and follow-up. We reviewed the AN's history and prospected its future managements.

Therapeutic effects of intravenous urapidil in elderly patients with hypertension and acute decompensated heart failure: A pilot clinical trial.

Urapidil has been proposed to be an effective vasodilator for the treatment of acute decompensated heart failure (ADHF); however, its effect on cardiac function, as compared with that of nitroglycerin, in elderly patients with hypertension and ADHF has yet to be determined. In the present study, a multicenter, open-label clinical trial was performed, in which 120 elderly patients with hypertension and ADHF were randomly assigned to the treatment (50-400 µg/min intravenous urapidil) or control group (5-40 µg/min intravenous nitroglycerin). The dosages of the medications were adjusted according to the blood pressure of the patients. The systolic and diastolic blood pressure, heart rate and serum level of N-terminal pro B-type natriuretic peptide (NT-proBNP) were evaluated at hospital admission and at days 1, 2, 3 and 7 after treatment. In addition, the left ventricular function was assessed by measuring the left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume at hospital admission and at days 2 and 7 after treatment. The results indicated that intravenous administration of urapidil and nitroglycerin were effective in lowering the blood pressure and heart rate within 7 days, with no significant differences observed between the two groups (P>0.05). By contrast, greater reduction in the serum NT-proBNP level (2,410.4±546.1 vs. 4,234.1±876.4 pg/ml; P<0.05) and greater improvement in the LVEF (55.3±3.4 vs. 45.2±2.4%; P<0.05) were observed in the urapidil-treated group, as compared with the nitroglycerin-treated group. No adverse events were reported during the treatment period in the two groups. The clinical outcomes at 6 months following discharge were evaluated and were not found to be significantly different between the two groups. In conclusion, the present results of the present study suggested that urapidil was as effective as nitroglycerin in controlling blood pressure and heart rate and was more effective in improving cardiac systolic function in elderly patients with hypertension and ADHF.