[Relationship between the neutrophil-to-lymphocyte ratio and estimated glomerular filtration rate in patients with primary aldosteronism: a cross-sectional study].

Objective: To investigate the associations between neutrophil-to-lymphocyte ratio (NLR) and estimated glomerular filtration rate (eGFR) in patients with primary aldosteronism (PA). Methods: This study was a cross-sectional study. Consecutive patients diagnosed with PA and admitted to the Second Affiliated Hospital of Nanchang University from October 2017 to April 2022 were enrolled. General information, blood routine, renal function, and other clinical data of the patients were collected. Based on the median NLR of the enrolled patients, NLR

An angular-resolved scattered-light diagnostic for laser-plasma instability studies.

We developed an angular-resolved scattered-light diagnostic station (ARSDS) to extend the study of laser-plasma instabilities (LPIs) by simultaneously diagnosing their features at different angles in a single shot. The ARSDS angularly samples the scattered light using an array of fibers with flexible setups. The collected light is detected with an imaging spectrometer, a streaked spectrometer, or a fiber-optic spectrometer to provide time-integrated/time-resolved spectral information. The ARSDS was implemented at Shenguang-II Upgrade laser facility for the double-cone ignition campaigns. Preliminary results confirm the importance of an angular-resolved detection due to the angular dependence of LPI processes, such as stimulated Raman scattering.

Clinical and sonographic features for the preoperative prediction of lymph nodes posterior to the right recurrent laryngeal nerve metastasis in patients with papillary thyroid carcinoma.

OBJECTIVE: To evaluate clinical and sonographic features predictive of lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) metastasis in patients diagnosed with papillary thyroid carcinoma (PTC). METHODS: We retrospectively reviewed the clinical records and ultrasound (US) images of 479 consecutive PTC patients who received total thyroidectomy or right lobectomy with central neck dissection (CND) between October 2017 and October 2019. Univariate and multivariate analyses were performed to identify clinical and sonographic features associated with LN-prRLN metastasis. Receiver operating characteristic (ROC) analysis was applied to evaluate the efficacy of clinical and sonographic features in the preoperative prediction of LN-prRLN metastasis. RESULTS: Overall, 127 (26.5%) patients had LN-prRLN metastasis. Multivariate logistic regression analysis showed that age < 45 years (p = 0.005; OR 2.155; 95% CI 1.262-3.683), male sex (p = 0.043; OR 1.657; 95% CI 1.016-2.704), tumor diameter > 1 cm (p = 0.042; OR 1.702; 95% CI 1.019-2.842), microcalcifications (p = 0.022; OR 1.980; 95% CI 1.104-3.551), and US-detected lateral compartment lymph node (LLN) metastasis (p = 0.001; OR 2.578; 95% CI 1.500-4.430) were independent risk factors for LN-prRLN metastasis. ROC analysis revealed that the multivariate logistic regression model had good accuracy in predicting LN-prRLN metastasis, with an area under the ROC curve of 0.758. CONCLUSIONS: Age less than 45 years, male sex, tumor diameter larger than 1 cm, microcalcifications, and US-detected LLN metastasis may preoperatively predict LN-prRLN metastasis.

Measurement of the cosmic ray proton spectrum from 40 GeV to 100 TeV with the DAMPE satellite.

The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1/2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.

[Value of intravoxel incoherent motion diffusion weighted imaging in evaluating the microstructure changes in white matter hyperintensities].

Objective: To investigate the value of intravoxel incoherent motion diffusion weighted imaging (IVIM DWI) in evaluating microstructure changes in elderly white matter hyperintensities (WMH) patients and to analyze the correlation between IVIM parameters and severity grading and cognitive scores. Methods: Sixty-two WMH patients in Zhejiang Hospital were collected from December 2014 to March 2018 and underwent conventional magnetic resonance (MR) plain scan and diffusion weighted imaging with different b values. The age was 60-92(74±10) years with 37 males, 25 females. The severity of WMH was assessed by T(2) fluid attenuated inversion recovery (FLAIR) sequence and Fazekas score,which were divided into two subgroups. Slow diffusion coefficient (D), fast diffusion coefficient (D(*)) and perfusion fraction (f) from IVIM parameters of double exponential model were compared between regions of WMH (deep WMH (DWMH) and periventricular WMH (PWMH)) and surrounding normal white matter (NWM).The Shapiro-Wilk test was used for normality tests, Kruskal-Wallis tests and Dwass-Steel-Critchlow-Fligner (DSCF) procedure were used for the comparison among these parameters. Furthermore, Wilcoxon two-sample test was used for the comparisons between different severity. Pearson correlation analysis was performed to determine whether these D, D(*), f values were correlated with the mini mental state examination (MMSE) scores. Results: D(D)WMH (0.83(0.72,0.99)×10(-3) mm(2)/s), D(PWMH)((1.13±0.25)×10(-3) mm(2)/s) were significantly higher than D(NWM) ((0.71±0.05)×10(-3) mm(2)/s)(P<0.01). f (DWMH) ((8.94%(7.46%,11.67%)), f (PWMH)(8.34%(6.73%,9.96%)) were significantly higher than f (NWM)(6.71%±1.72%)(P<0.01).D in DWMH were significantly lower than that in PWMH(P<0.01), there's no statistically difference between other groups. D in severe WMH (both DWMH and PWMH) were significantly higher than that in mild WMH (P=0.000 1, P=0.04). Only f in PWMH were positively associated with the MMSE scores (r=0.326 5,P<0.05). Conclusions: IVIM DWI can noninvasively assess the variation of microstructure diffusion and perfusion in WMH in one sequence,which may objectively reflect the severity of these lesions. This method has important clinical significance for better assessment and management of this disease.

[Correlations between gastric Helicobacter pylori infection and colorectal polyps or cancer].

Objective: To investigate the correlations between gastric Helicobacter pylori (Hp) infection and colorectal polyps or cancer. Methods: Among patients who finished colonoscopy exams in Peking Union Medical College Hospital (PUMCH) between May 2012 and May 2017, 3 483 patients were diagnosed with colorectal polyps, 135 patients with newly diagnosed colorectal cancer. A total of 1 925 healthy subjects were enrolled as normal controls. Gastric rapid urease tests (RUT) were done in all patients. General clinical data, RUT results, sizes and numbers of polyps, cancer location were analyzed. Results: The proportion of Hp infection in patients with colorectal polyps was 31.5%, higher than that in healthy controls. The odds ratio (OR) of Hp infection in polyp group was 1.17 (95%CI 1.04-1.32) after age and gender were adjusted. The Hp infection rate in patients with polyps over or equal to 1 cm was significantly higher than that in patients with polyps smaller than 1 cm. Patients with more than 1 polyps presented a higher rate of Hp infection than patients with only 1 polyp. Hp infection rate in patients with colorectal cancer was 36.3%, with the adjusted OR 1.56 (95%CI 1.06-2.30). The location of colorectal cancer was not correlated with Hp infection. Conclusions: Gastric Hp infection is more common in patients with colorectal polyps than in healthy controls. Polyps ≥1 cm, multiple polyps and colorectal cancer are correlated with higher rates of Hp infection. Cancer location is irrelevant to Hp infection.

[Clinical features and expression of PLA(2)R in renal tissue with idiopathic membranous nephropathy in children].

Objective: To explore the clinical features and expression of PLA(2)R in renal tissue of children with idiopathic membranous nephropathy. Methods: Retrospective study was performed in patients with membranous nephropathy diagnosed through renal biopsy and the follow-up time was at least half a year in Shanghai Children's Hospital from January 2010 to February 2017. We compared their clinicopathological and pathological findings of IMN. Indirect immunofluorescence assay was used to detect glomerular PLA(2)R expression. We analyzed the differences of clinical features between the PLA(2)R negative and positive groups. T test, rank-sum test and Fisher exact test were used. Results: Eleven cases had hematuria and proteinuria, 9 cases presented with nephrotic syndrome, and 2 cases showed isolated proteinuria. Of the 22 cases of children with IMN, 16 patients had complete remission (complete remission rate was 72.8%), and 22 patients had partial remission. The renal function of all cases was normal and in all cases the estimated glomerular filtration rate was > 90 ml/(min·1.73m(2)). Of 22 cases with IMN, 7 cases were PLA(2)R-positive in renal tissue and 15 cases were PLA(2)R-negative. The age of positive group (10 years old) was older than the negative group (6 years old)(Z=-2.483, P<0.05) and the time of positive group (6 months) for urine protein to return to negative was longer than the negative group (2.5 months) through treatment. These differences were significantly different (Z=-2.072, P<0.05). Conclusions: Hematuria and proteinuria can be found in most children with idiopathic primary membranous nephropathy. Prednisone combined with immunosuppressant was effective. The positive rate of PLA(2)R in renal tissue of children with IMN was about 32%. The age of PLA(2)R positive group was older than the negative group. And the time of urine protein turning to negative in positive group was longer than that in the negative group.

[Prevalence and influential factors of stroke in Jiangxi Province in 2014].

Objective: To discuss the prevalence and influential factors of stroke among population in Jiangxi Province. Methods: Four cities in urban areas and four counties in rural areas were selected firstly, in which two districts or townships were selected; and then three communities or villages were chosen from each district and township, respectively, using the simple random sampling (SRS) method. Finally 15 269 subjects aging 15 years old or above, living in Jiangxi Province ≥6 months were randomly selected to participate in this survey from November 2013 to August 2014. Information of population characteristics, life behavior way, individual disease history were collected through questionnaire survey, and height, weight, waist circumference, blood pressure, body fat rate, visceral fat index and so on were measured by instruments. Risk factors of stroke prevalence were analyzed by the unconditioned logistic regression analysis. Results: A total of 15 269 participants (6 267 males) from 15 364 eligible participants were included in the statistical analysis. Out of which, 7 793 participants came from urban areas, and their average age was (53.04±17.91) years old. In this study, 226 stroke patients (117 males) were found among15 269 participants, including 122 urban participants and 104 rural participants, whose average age was (67.76±9.74) years old. The prevalence of stroke was 1 480.12/100 000 in 2014, which was separately 1 866.92/100 000 and 1 210.84/100 000 among males and females. The prevalence of people aging (45-49) years old was 413.79/100 000 (6/1 450) , while which among people aging 75 years old and above was 3 311.62/100 000 (61/1 842) . The prevalence of stroke among residents in Jiangxi presented an uprising tendency with age increasing (linear-by-linear association χ(2)=62.23, P<0.01). The research showed that when other influencing factors including gender, BMI, waist circumference, pulse-pressure difference, VAI, and sleeping time in non-working days were controlled, hypertensive patients had a higher risk of stroke than people without hypertension (OR=6.88, 95%CI: 4.90-9.67), drinkers had a higher risk of stroke than non-drinkers (OR=1.56, 95%CI: 1.17-2.08), compared with people <65 years old, people aged 65-74 years old and ≥75 years old had a higher risk of stroke, the value of OR (95%CI) were 1.88 (1.36-2.59) and 1.97 (1.39-2.80), respectively, compared with people with normal body fat percentage, people whose body fat percentage on high side and people who with high body fat percentage had a higher risk of stroke, the value of OR (95%CI) were 1.71 (1.18-2.48) and 1.74 (1.18-2.56), respectively, people with sleep time >8 h had a higher risk of stroke than those with sleep time of 6-8 h. Conclusion: There was a high stroke prevalence among residents in Jiangxi province. Hypertension, drinking, age, BFP and sleep duration were associated with stroke prevalence. Corresponding measures for high-risk population and risk factors should be strengthened to prevent and control the stroke.

Rapamycin facilitates fracture healing through inducing cell autophagy and suppressing cell apoptosis in bone tissues.

OBJECTIVE: To investigate the changes in cell autophagy and the molecular mechanism of rapamycin affecting the fracture healing. MATERIAL AND METHODS: Sprague-Dawley (SD) rats were used to establish the right femoral shaft fracture models, and then underwent immunofluorescence assay to detect the autophagy level in bone tissues. After model establishment, SD rats were divided into two groups, the control group and the rapamycin group (1 mg/kg/d). Respectively, at the 2nd, 4th, and 6th week, rats were randomly selected from each group for X-ray and Micro-computed tomography (Micro-CT) examinations to determine callus growth, immunofluorescence assay to detect the protein expression of light chain 3 II (LC3 II), immunohistochemistry to evaluate the autophagy level through detecting the expression of Beclin1 in rats, Western blotting assay to detect cell apoptosis in tissues, hematoxylin and eosin staining (HE staining) to evaluate the osteoblastic activity through count of osteoblast in bone tissue at the end of fracture, and measure the expression of vascular endothelial growth factors (VEGF). RESULTS: Significant increases were seen in protein expression of cells in bone tissues at the end of fracture. In rapamycin group, callus formation and calcification level in rats were all higher than those in control group; compared with control group, for rats in rapamycin group, cell autophagy was significantly elevated in bone tissues, while cell apoptosis at the end of fracture was reduced with a significant increase in osteoblastic activity. The expression of VEGF in rapamycin group was higher than that in control group. CONCLUSIONS: Rapamycin can facilitate fracture healing through inducing cell apoptosis and suppressing cell apoptosis in bone tissues.

Melatonin promotes osteoblast differentiation of bone marrow mesenchymal stem cells in aged rats.

OBJECTIVE: The current study was to explore the effect of melatonin on osteoporosis and relevant mechanisms. MATERIALS AND METHODS: We performed micro-CT to detect bone microstructure and ELISA to detect the contents of osteocalcin (OCN) and bone alkaline phosphatase (BAP) in serum. Double fluorescence labeling of calcein and tetracycline and toluidine blue staining were used to determine morphological indexes of bone tissues. Alizarin red staining and Oil Red O staining were performed to recognize bone cells and adipocytes. RT-PCR was performed to determine the expression of osteoblast differentiation related genes. RESULTS: In the current study, data from micro-CT indicated that melatonin significantly increased the bone mass density (BMD), bone volume/tissue volume (BV/TV), trabecular number (Tb.N) and trabecular thickness (Tb.Th), and decreased the Structure Model Index (SMI) and trabecular Separation/Spacing (Tb.Sp) in elderly rats. Melatonin reduced calcium and phosphorus losses in urine and increased BAP and OCN levels in serum in elderly rats and increased bone formation rate (BFR) and bone mineralization rate (MAR) in elderly rats. Melatonin increased the number of osteoblasts in bone marrow and reduced the number of adipocytes in elderly rats. Melatonin also promoted the expression of osteogenic differentiation genes and suppressed the expression of adipogenic differentiation genes. CONCLUSIONS: WE suggest that melatonin could alleviate osteoporosis in aged rats' models probably by promoting osteoblast differentiation.

[Study on the impact of labro-chondral complex on development of the acetabulum after close reduction in developmental dysplasia of the hip].

Objective: To explore the influence of the labro-chondral complex (LLC) on the development of the acetabulum after close reduction in developmental dysplasia of the hip (DDH). Methods: Sixty-one cases (72 hips) with DDH presented in Beijing Jishuitan Hospital were reviewed, all the patients were treated by closed reduction, arthrogram and Spica casting from March 2010 to December 2013. The anterior-posterior pelvic radiography was performed to evaluate the morphology of the labro-chondral complex and reduction of the hip. The cases were divided into Ⅰ, Ⅱ, Ⅲ, Ⅳ four groups according to the shape of the LLC initially, and when performed the secondary Spica cast after 3 months, these cases were divided into 0-0.4, 0.4-0.6, and >0.6, three groups based on the height difference ratio (HDR) of the LLC. The relationship between the shape and HDR of the LLC was analyzed. The AI and CE angle were used to evaluate development of the hip during the latest follow up. The impact of the shape and HDR of the LLC on the development of the acetabulum was explored as well. Results: The HDR was the least in the type Ⅰ hips, all cases were less than 0.6, the AI in this group was significantly lower than the others(24.33°±3.12°), and the CE angle was significantly higher in the type Ⅰ hips(15.22°±3.11°) during the latest follow up. The CE angle was significantly different among the three groups of HDR. The HDR was lower, the CE angle was higher. The AI in 0-0.4 group was significantly lower than the others(14.24°±3.10°). Conclusion: The shape of the LLC is helpful to judge development of the acetabulum when closed reduction was performed in DDH. And the HDR in the secondary cast change could be used as a sensitive index to predict development of the hip.

Detection and sequence analysis of grapevine virus B isolates from China.

The presence of grapevine virus B (GVB) was detected in 188 grapevine samples from China by double antibody sandwich ELISA (DAS-ELISA) and reverse transcription-PCR (RT-PCR). The accuracy of detection by RT-PCR was confirmed by sequencing amplified PCR fragments. Seventeen samples were GVB-positive by DAS-ELISA and five by RT-PCR. The isolate QMW proved to be positive by RT-PCR only, and four isolates (DGWH, DGW, QM, and JFL) could be detected by both methods. Among the five GVB-positive samples detected by RT-PCR, two isolates were originally collected from Henan province and three from Liaoning province. The expected 722 bp DNA fragment, covering partial ORF3 through partial ORF5, was amplified from the five GVB infected samples. Sequence analysis revealed that the molecular variants΄ composition of GVB in the different isolates was complex. Clones of DGWH, DGW, QM, and JFL isolate shared high nucleotide identities, while the identities among the clones of isolate QMW varied. The variants of GVB isolates obtained in this study showed nucleotide identities from 81.1% to 97.9% among themselves, and 79.1% to 98.5% identity with five previously published GVB isolates in NCBI. The alignment of partial ORF3 and the phylogenetic relationships of ORF4 revealed that the molecular variants of Chinese GVB isolates could be clustered into three groups. Only isolate DGW was in the same group with the reported GVB isolates from other countries; the other four GVB isolates in this study were clustered into two groups.

Co-transfection of adeno-associated virus-mediated human vascular endothelial growth factor165 and transforming growth factor-ß1 into annulus fibrosus cells of rabbit degenerative intervertebral discs.

Intervertebral disc degeneration is a common condition that may lead to low back pain and radiculopathy. Understanding the pathophysiology and cellular and molecular events of degenerative disc disease has resulted in the proposal of a gene therapy approach to halt and reverse disc degeneration. We explored the feasibility of reversing intervertebral disc degeneration using human vascular endothelial growth factor165 (hVEGF165) and transforming growth factor-ß1 (TGF-ß1) gene therapy. hVEGF165 complementary DNA was obtained from pcDNA3(+)-hVEGF165 and cloned into adeno-associated virus (AAV)-pSNAV plasmids to construct the recombinant plasmid, AAV-pSNAV-hVEGF165. After identification through restriction enzyme digestion and DNA sequencing, the AAV-pSNAV-hVEGF165 was transfected into HEK293 cells and vascular endothelial cells. Protein expression of hVEGF165 was detected using a fluorescent immunohistochemical assay, and the effect of hVEGF165 on vascular endothelial cell proliferation was determined with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Packaged AAV-hVEGF165 and AAV-TGF-ß1 were co-transfected into the annulus fibrosus cells of degenerative intervertebral discs. hVEGF165 and TGF-ß1 expression by annulus fibrosus cells and the effect of the co-transfection on the level of collagen type I protein expression by annulus fibrosus cells were detected with Western blot. The results of restriction enzyme digestion and DNA sequencing confirmed that AAV-pSNAV-hVEGF165 plasmids were constructed. The fluorescent immunohistochemical results confirmed hVEGF165 protein expression. The MTT results showed that the hVEGF165 protein promoted vascular endothelial cell proliferation. Biologically active AAV-hVEGF165 and AAV-TGF-ß1 were successfully constructed. Western blot confirmed hVEGF165 and TGF-ß1 expression in annulus fibrosus cells and demonstrated that the level of collagen type I protein expression was significantly higher in annulus fibrosus cells co-transfected with both AAV-hVEGF165 and AAV-TGF-ß1 compared with that in cells transfected with AAV-hVEGF165 or AAV-TGF-ß1 alone. hVEGF165 has a synergistic effect with TGF-ß1 that promotes the expression of collagen type I protein in annulus fibrosus cells from degenerative intervertebral discs.

First Report of Grapevine leafroll-associated virus 4 and 5 in Grapevines in China.

Grapevine leafroll disease (GLD) is one of the most important diseases of grapevines worldwide. Nine serologically distinct viruses in the Closteroviridae family are associated with GLD. Previous studies reported that Grapevine leafroll-associated virus (GLRaV) -1, -2, -3, and -7 were present in grapevines in China with GLRaV-1 and -3 the predominant viruses associated with GLD (1). To confirm if GLRaV-4 and -5 were also present in China, 36 dormant canes from individual vines of 29 cultivars that showed GLD leaf symptoms during the growing season were collected from the germplasm collection plot of the Research Institute of Pomology, Chinese Academy of Agricultural Sciences. Total RNA extracted by a silica capture protocol (2) from phloem-enriched bark of 36 samples was tested separately for GLRaV-4 and -5 by reverse transcription (RT)-PCR using virus-specific primers. Primers LR4F (5'-ACATTCTCCACCTTGTGCTTTT-3') and LR4R (5'-CATACAAGCGAGTGCAATTAC-3') (4) were used to amplify a 321-bp fragment corresponding to a partial region of the HSP70 gene from GLRaV-4. One sample from cv. Autumn Royal was infected by GLRaV-4. The amplicon was cloned and a single clone was sequenced (GenBank Accession No. GQ246624) that showed 99% nucleotide identity with a corresponding region of a GLRaV-4 isolate from the United States (Accession No. AF039553). Since antiserum specific to GLRaV-4 was unavailable, a second pair of primers, LR4CP-F (5'-GGTGTCCAGCGCTTCCAA-3') and LR4CP-R (5'-GCCAGAGAAGCATCGTAA-3'), was designed on the basis of the sequence of GLRaV-4 from Chile (Accession No. EU746620) that amplified a 300-bp fragment specific to the coat protein gene of GLRaV-4. The amplicon was cloned and a single sequence (Accession No. GQ479041) was compared with a corresponding nucleotide sequence of GLRaV-4 from Chile (Accession No. EU746621) showing 99% identity. A sample from cv. Malaga Rose was positive when tested by ELISA with antibodies specific to GLRaV-5 (Neogen Europe, Ltd. Scotland, UK) and this was confirmed by amplification of a 690-bp fragment corresponding to the GLRaV-5 coat protein gene using virus-specific primers LR5F (5'-CCCGTGATACAAGGTAGGACA-3') and LR5R (5'-CAGACTTCACCTCCTGTTAC-3') (3). The amplicon was cloned and a single clone was sequenced (Accession No. GQ246625) that showed 95% nucleotide identity with the CP gene sequence of GLRaV-5 from Argentina (Accession No. EU815935). To our knowledge, this is the first report of GLRaV-4 and -5 in grapevines in China. Confirmation of these viruses in China is very important for producing virus-free plants and this information also will be helpful in developing a multiplex RT-PCR assay to simultaneously detect multiple GLRaVs and helpful with studies on the molecular variability of these viruses. References: (1) Y. Dong et al. China Fruits 6:9, 2005. (2) X. Foissac et al. Acta Hortic. 550, 37, 2001. (3) X. Good and J. Monis. Phytopathology 91:274, 2001. (4) F. Osman et al. J. Virol. Methods 141:22, 2007.

Aliskiren prevents cardiovascular complications and pancreatic injury in a mouse model of obesity and type 2 diabetes.

AIMS/HYPOTHESIS: The effect of renin inhibition on type 2 diabetes is still unclear. The present study was undertaken to examine the efficacy of aliskiren, a direct renin inhibitor, on cardiovascular injuries, glucose intolerance and pancreatic injury in a mouse model of type 2 diabetes. METHODS: Groups of db/db mice, with obesity and type 2 diabetes, were treated with aliskiren (3, 6, 12 and 25 mg kg(-1) day(-1)) or hydralazine (80 mg kg(-1) day(-1)) for 6 weeks, and the protective effects were extensively compared among groups. RESULTS: All sub-pressor and hypotensive doses of aliskiren significantly attenuated cardiac fibrosis, macrophage infiltration and coronary remodelling, and improved vascular endothelial function in db/db mice. These protective effects of aliskiren were attributed to the attenuation of cardiac p22(phox)-related NADPH oxidase-induced superoxide and the restoration of vascular endothelial nitric oxide synthase (eNOS) production. Aliskiren at the highest dose (25 mg kg(-1) day(-1)), but not at lower doses, partially reduced glucose intolerance in db/db mice. Furthermore, the highest dose of aliskiren significantly attenuated the decreases in pancreatic islet insulin content and beta cell mass, and prevented pancreatic islet fibrosis in db/db mice, being associated with the reduction of 8-hydroxy-2'-deoxyguanosine-positive cells and Nox2 (also known as Cybb) expression in pancreatic islets by aliskiren. CONCLUSIONS/INTERPRETATION: Our work provides the first evidence that direct renin inhibition with aliskiren protects against cardiovascular complications and pancreatic injury, through the attenuation of oxidative stress. Thus, we propose that aliskiren may be a promising therapeutic agent for type 2 diabetes.

Runx2-mediated activation of the Bax gene increases osteosarcoma cell sensitivity to apoptosis.

The Runx family of transcription factors regulate cell growth and differentiation, and control the expression of target genes involved in cell fate decisions. We examined the role of the bone-related member of this family, Runx2, in regulating apoptosis via modulation of the Bcl2 family of genes in the osteosarcoma cell line Saos2. Our data demonstrate that Runx2 directly binds to two Runx-specific regulatory elements on the human bax promoter thereby inducing Bax expression. Furthermore, bone morphogenetic protein-induced or vector-mediated expression of Runx2 resulted in upregulation of Bax expression, and subsequent increased sensitivity of Saos2 cells to apoptosis. Finally, the observed upregulation of Bax expression and increased apoptosis were Runx2 dependent as Runx2 loss of function abrogated these effects. Our study provides the first evidence for Bax as a direct target of Runx2, suggesting that Runx2 may act as a proapoptotic factor in osteosarcoma cells.

Morphine applied to the thalamic nucleus submedius produces a naloxone reversible antinociceptive effect in the rat.

Our previous studies have indicated that the thalamic nucleus submedius (Sm) is involved in nociceptive modulation and plays an important role in an endogenous analgesic system (a feedback loop) consisting of spinal cord - Sm - ventrolateral orbital cortex (VLO) - periaqueductal gray (PAG) - spinal cord. To further investigate the neurotransmitter and receptor mechanisms in this nociceptive modulatory pathway, we tested the effects of microinjection of morphine and naloxone into the Sm on the rat tail flick (TF) reflex. A unilateral microinjection of morphine (8.0 mM, 0.5 microl) into the Sm significantly depressed the TF reflex, whereas a unilateral microinjection of naloxone (5.0 mM, 0.5 microl) into the Sm facilitated the TF reflex. Five minutes after morphine application into Sm, injection of naloxone in this nucleus markedly reversed the inhibition evoked by applying morphine in Sm. These findings suggest that the endogenous opioid peptides may be involved in the antinociceptive effects evoked by activation of the Sm-VLO-PAG pathway which depressed the nociceptive inputs at the spinal level via the brainstem descending inhibitory system, and exert a tonic descending influence.