rAAV9-mediated supplementation of miR-29b improve angiotensin-II induced renal fibrosis in mice.

BACKGROUND: Renin-angiotensin-aldosterone system activation is the critical factor in renal remodeling and dysfunction. Our previous study suggested that miR-29b may attenuate AngII-induced renal intestinal fibrosis in vitro. In the present study, we aimed to determine whether recombinant rAAV9-mediated miR-29b delivery protects against AngII-induced renal fibrosis and dysfunction. METHOD: Mice were treated with AngII via osmotic mini-pumps, or phosphate-buffered saline. rAAV9 vectors were produced using the rBac-based system in SF9 cells. rAAV9-miR-29b or rAAV9-control-miR was injected into the kidneys of mice subjected to the model of AngII infusion. The role of miR-29b in renal fibrosis was assessed using quantitative polymerase chain reaction, western blot, and histology. RESULTS: In AngII-induced fibrotic kidney tissue, miR-29b expression was downregulated. rAAV9-miR-29b delivery significantly reversed renal injury as indicated by decreased serum creatinine and injury related gene expression in AngII-infused mice. Regarding organ remodeling, tubulointerstitial fibrosis and deposition of extracellular matrix components such as collagen type I and type III were significantly decreased in renal tissue from mice delivered rAAV9-miR-29b. CONCLUSION: Our results demonstrate great potential for use of rAAV9 as an applicable vector for delivery of miR-29b as an antifibrogenic factor for treatment of tubulointerstitial fibrosis-induced renal injury.

Identification and analysis of chemosensory genes encoding odorant-binding proteins, chemosensory proteins and sensory neuron membrane proteins in the antennae of Lissorhoptrus oryzophilus.

The rice water weevil, Lissorhoptrus oryzophilus Kuschel (Coleoptera: Curculionidae), is a destructive pest that causes damage to rice crops worldwide. The olfactory system is critical for host or mate location by weevils, but only limited information about the molecular mechanism of olfaction-related behaviour has been reported in this insect. In this study, we conducted SMRT-seq transcriptome analysis and obtained 54,378 transcripts, 38,706 of which were annotated. Based on these annotations, we identified 40 candidate chemosensory genes, including 31 odorant-binding proteins (OBPs), six chemosensory proteins (CSPs) and three sensory neuron membrane proteins (SNMPs). Phylogenetic analysis showed that LoryOBPs, LoryCSPs and LorySNMPs were distributed in various clades. The results of tissue expression patterns indicated that LoryOBPs were highly abundant in the antennae, whereas LoryCSPs were highly abundant not only in the antennae but also in the abdomen, head and wings. Our findings substantially expand the gene database of L. oryzophilus and may serve as a basis for identifying novel targets to disrupt key olfactory genes, potentially providing an eco-friendly strategy to control this pest in the future.

Spironolactone suppresses aldosterone-induced Kv1.5 expression by attenuating mineralocorticoid receptor-Nox1/2/4-mediated ROS generation in neonatal rat atrial myocytes.

Our previous investigation indicated that angiotensin II (Ang II) enhances the expression of Kv1.5, a promising target for the treatment of atrial fibrillation (AF), by activating reactive oxygen species (ROS)-dependent phosphorylation of Smad 2/3 (forming P-Smad 2/3) and ERK 1/2 (forming P-ERK 1/2). A recent study indicated that aldosterone (Aldo) upregulates atrial Kv1.5 protein in a rat AF model, but the mechanism remains unknown. The present study aimed to clarify the mechanism underlying Aldo-induced Kv1.5 expression and to test whether spironolactone may modulate atrial Kv1.5. Our Western blot analysis indicated that the Aldo/mineralocorticoid receptor (MR) interacts with Ang II/AT1R in upregulating Kv1.5 expression in cultured neonatal atrial myocytes (NRAMs). Blockade of MR with spironolactone and of AT1R with losartan significantly suppressed Kv1.5 expression induction by combined Aldo and Ang II treatment. Aldo increased the protein expression of Nox1, Nox2 and Nox4, but this effect was abolished by spironolactone pretreatment. The Aldo-induced upregulation of Kv1.5 was also reversed by the Src protein tyrosine kinase family inhibitor PP2, the Nox2 inhibitor gp91ds-tat and the Nox1/Nox4 inhibitor GKT137831 but not by the Rac GTPase inhibitor NSC23766. Flow cytometry showed that the Aldo-induced ROS production was inhibited by spironolactone, PP2, gp91ds-tat and GKT137831. Spironolactone suppressed the Aldo-induced protein expression phosphorylated Src (P-Src), P-Smad 2/3 and P-ERK 1/2. In conclusion, we have demonstrated that spironolactone suppresses Aldo-induced Kv1.5 expression by attenuating MR-Nox1/2/4-mediated ROS generation in NRAMs.

Inhibition of perivascular mast cell activation is involved in the atheroprotective effect of rosiglitazone in apolipoprotein E-deficient mice.

Activation of perivascular mast cells (MCs) and subsequent release of their abundant inflammatory mediators have been well documented to induce excessive inflammation and subsequent rupture of atherosclerotic plaques. Previous studies have suggested that rosiglitazone affects the stability of plaques, although the precise mechanism of action is not clearly understood. In this study, we evaluated the effects of rosiglitazone on MCs in vivo and in vitro. Apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat diet (HFD), with or without rosiglitazone supplemented in the drinking water (1.5 mg/kg/day). Compared with the HFD group, rosiglitazone did not affect blood glucose levels, but it attenuated serum levels of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6), ameliorated plaque lipid accumulation and the expression of matrix metalloproteinases-2 and -9, increased the collagen content of plaques, and inhibited perivascular MC degranulation and chymase expression. The in vitro experiments showed that rosiglitazone treatment repressed the expression of TNFα and IL-6 induced by antigen-challenged RBL-2H3 cells in a peroxisome proliferator-activated receptor γ (PPARγ)-independent manner, which was related to the repression of protein kinase C (PKC)-ß1 activation. Combined, these results suggest that the plaque-stabilizing effect of rosiglitazone is attributable to its ability to inhibit the activation of perivascular MCs.

Correction to: Development of a new risk nomogram of perioperative major adverse cardiac events for Chinese patients undergoing colorectal carcinoma surgery.

On this article the authors requested to add another affiliation which is Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510,080, China for Juhong Zhang, Xiuren Gao and Zhibin Huang. The new affiliation is now added in this article. The remainder of the article remains unchanged.

Expression profile changes of cytochrome P450 genes between thiamethoxam susceptible and resistant strains of Aphis gossypii Glover.

Cytochrome P450 monooxygenases represent a key detoxification mechanism in neonicotinoids resistance in Aphis gossypii Glover. Synergism analysis has indicates that P450s are involved in thiamethoxam resistance. In this study, expression changes in the transcripts of P450 genes were determined in thiamethoxam-susceptible and thiamethoxam-resistant strains. Nine P450 genes in CYP3 clade were significantly overexpressed in the resistant strain (especially CYP6CY14, which was increased 17.67-fold) compared with the susceptible strain. Transcripts of ecdysone synthesis-related P450 genes, including CYP302A1, CYP306A1, CYP307A1 and CYP315A1, were up-regulated in the resistant strain, which may accelerate molting hormone production. The ecdysone response genes (ecdysone receptor (EcR), ultra-spiracle (USP) and Broad-complex protein (Br-C)) were overexpressed in the resistant strain. RNA interference (RNAi) targeting CYP6CY14 significantly increased the sensitivity of the resistant aphid to thiamethoxam. The results of the present study indicate the possible involvement of these P450 genes in thiamethoxam resistance. Our findings may facilitate further work to validate the roles of these P450s in thiamethoxam resistance based on heterologous expression, and show that screening the expression changes in P450 genes can reveal the impact of thiamethoxam on ecdysone synthesis-related P450 genes. These results are useful for understanding the mechanism of thiamethoxam resistance and will contribute to the management of insecticide-resistant cotton aphids in China.

H2S inhibits angiotensin II-induced atrial Kv1.5 upregulation by attenuating Nox4-mediated ROS generation during atrial fibrillation.

Our previous study demonstrated that angiotensin II (Ang II) upregulates the expression of Kv1.5, a promising target for atrial fibrillation (AF) therapy, by activating ROS-dependent P-Smad2/3 and P-ERK 1/2. A recent study showed that hydrogen sulfide (H2S) may modulate the effects of angiotensin II (Ang II) by inhibiting the NADPH oxidase 4 (Nox4)-ROS signaling in the heart. The present study aimed to determine whether H2S is involved in the regulation of atrial Kv1.5 via ROS-related mechanisms in AF. Cultured neonatal rat atrial myocytes and a beagle model of AF were used for this study. In the neonatal rat atrial myocytes, quantitative PCR and enzyme immunoassays revealed that the mRNA expression levels of angiotensinogen, angiotensin-converting enzyme, and Ang II type I receptor (AT1R) and the Ang II supernatant concentration were significantly increased by hydrogen peroxide (H2O2) incubation, and these H2O2-induced alterations were reversed by diphenyleneiodonium, apocynin and H2S supplementation. Flow cytometry and Western blotting revealed that blockade of H2S biosynthesis using dl-propargylglycine increased ROS production and the expression of Ang II and Kv1.5. Sodium hydrosulfide (an exogenous H2S donor) and Nox4 siRNA inhibited Ang II-induced ROS production and Ang II-induced expression of Kv1.5, P-Smad2/3, P-ERK 1/2. Sodium hydrosulfide suppressed the Ang II-induced upregulation of Nox4. In our beagle AF model, 24 h of rapid atrial pacing (RAP) increased the atrial Ang II concentration, ROS production and the protein expression of Nox4, Kv1.5, P-Smad2/3 and P-ERK 1/2. These RAP-induced changes were inhibited by H2S supplementation and losartan (an AT1R blocker) pretreatment. In conclusion, our study indicates that H2S downregulates Ang II-induced atrial Kv1.5 expression by attenuating Nox4-related ROS-triggered P-Smad2/3 and P-ERK 1/2 activation during AF. H2S supplementation would be beneficial for AF treatment via the suppression of atrial Kv1.5 expression.

Development of a new risk nomogram of perioperative major adverse cardiac events for Chinese patients undergoing colorectal carcinoma surgery.

PURPOSE: The purpose of this study is to create a new risk nomogram to predict perioperative major adverse cardiac events in patients undergoing colorectal carcinoma surgery. METHODS: A total of 1899 patients who underwent colorectal carcinoma surgery at a tertiary teaching hospital in China between 2007 and 2012 were recruited. Logistic regression analysis was used to define risk factors for major adverse cardiac events. A nomogram-predicting model was built based on the logistic regression model and discrimination was tested by receiver operating characteristic curves. RESULTS: Fifty-six (2.9%) among 1899 included patients developed at least one cardiac event. Eight risk factors were found in the multivariate logistic regression model, which included age ≥60 years, smoking, a history of chronic kidney disease, coronary artery disease, congestive heart failure, hypertension, preoperative albumin levels ≤35 g/L, blood transfusion ≥500 mL, and intraoperative blood pressure variability. P = 0.708 in the Hosmer-Lemeshow test indicated acceptable calibration power. Based on this multivariate model, we built a risk nomogram model for these cardiac events with an area under the curve (95% confidence interval) of 0.923 (0.889, 0.957), which demonstrated good discrimination of this model. When the probability cutoff was 1.9% (total score of 83), the nomogram model had the best sensitivity and specificity in predicting cardiac events. CONCLUSIONS: A new nomogram model for predicting perioperative major adverse cardiac events in patients who had colorectal carcinoma surgery was established in this study. When the total score is >83, patients undergoing colorectal carcinoma surgery should be considered at high risk of perioperative major adverse cardiac events.

Identification and characterization of microRNAs expressed in antennae of Holotrichia parallela Motschulsky and their possible roles in olfactory regulation.

MicroRNAs (miRNAs) are small noncoding RNAs that play posttranscriptional, regulatory roles in various biological processes. However, there has been limited investigation into the potential function of miRNAs in olfaction. The coleopteran Holotrichia parallela is an economically important pest, and miRNAs have been identified in only one coleopteran (Tribolium castaneum). Therefore, this study was conducted to identify miRNAs expressed in the antennae of H. parallela and obtain insights into their possible roles in olfaction. By combining deep sequencing and miRDeep2 software, a total of 99 miRNAs, including 76 conserved miRNAs and 23 novel miRNAs, were identified from H. parallela antennae. The 76 conserved miRNAs belong to 63 families and the other 23 may be species specific or tissue specific. The identified miRNAs have many conserved features of miRNAs. Evaluation of the conservation of the identified miRNA families across different species revealed that most of the families are insect specific. The prediction and annotation of targets suggested that 13 of the identified miRNAs participate in olfactory regulation. Gender differences in antennal expression of nine of the olfactory-related miRNAs were confirmed by quantitative real-time PCR.

Identification and profiling of miRNAs in overwintering Lissorhoptrus oryzophilus via next-generation sequencing.

MicroRNAs (miRNAs) are important regulators of various biological processes in organisms. Insects subjected to abiotic stress can regulate gene expression post-transcriptionally through the use of microRNAs. However, the role of miRNAs in response to cold stress in Lissorhoptrus oryzophilus Kuschel remains unknown. The rice water weevil, L. oryzophilus, is an invasive insect that is able to survive cold winters. To characterize changes in miRNAs in response to overwintering in L. oryzophilus, a comprehensive comparative analysis of microRNAs was performed involving an overwintering and a normal adult. High-throughput Illumina sequencing and bioinformatics analyses revealed 121 conserved and 14 potential novel microRNAs in two small libraries. The novel miRNAs exhibit low expression levels in both libraries. After the expression profiles of the miRNAs in the two libraries were normalized, 36 miRNAs in L. oryzophilus were found to be differentially expressed in response to overwintering. In particular, 14 conserved miRNAs and 6 novel miRNAs were up-regulated, while 15 conserved miRNAs and 1 novel miRNA were down-regulated. In addition, the expression patterns of 11 conserved and potentially novel miRNAs were confirmed by quantitative RT-PCR analysis. Most importantly, this work provides a unique resource of characterized miRNAs for overwintering L. oryzophilus and contributes to studies of the functions of cold-related and other L. oryzophilus miRNAs.

Updated incidence rates and risk factors of esophageal cancer in Nan'ao Island, a coastal high-risk area in southern China.

Esophageal cancer (EC) is one of the most common cancers in China. The purpose of this study was to investigate the updated incidence rates and risk factors of EC in Nan'ao Island, where the EC incidence rate was chronically the highest in southern China. To calculate the annual incidence rate, data on 338 EC cases from Nan'ao Cancer Registry system diagnosed during 2005-2011 were collected. A case-control study was conducted to explore the EC risk factors. One hundred twenty-five alive EC patients diagnosed during 2005-2011 and 250 controls were enrolled into the case-control study. A pre-test questionnaire on demography, dietary factors, drinking water treatment, and behavioral factors was applied to collect information of all participants. The average EC incidence rates during 2005-2011 were 66.09/105, 94.62/105, 36.83/105 for both genders, males and females, respectively, in Nan'ao Island. The EC incidence rate in males was 2.40- to 4.55-fold higher than that in females in the period from 2006 to 2011 (P < 0.05). Considering the onset age, males tend to be much younger than females and reached peak incidence rate at a younger age (P < 0.05). Drinking water treatment by filter (odds ratio [OR] = 0.28, 95% confidence interval [95% CI] = 0.13-0.58) and fruit consumption (OR = 0.55, 95% CI = 0.32-0.94) reduced the risk for EC. On the contrary, the pickled vegetables consumption (OR = 2.64, 95% CI = 1.46-4.76) and liquor drinking (OR = 2.32, 95% CI = 1.21-4.44) increased the risk for EC. These results may be of importance for future research on EC etiology and prevention strategies.

DIFFERENTIAL PROTEOME ANALYSIS OF THE MALE AND FEMALE ANTENNAE FROM Holotrichia parallela.

To understand the olfactory mechanisms of Holotrichia parallela antennae in detecting volatile compounds in the environment, protein profiles of H. parallela antennae were analyzed using two-dimensional electrophoresis followed by mass spectrometry and bioinformatics analyses. Approximately 1,100 protein spots in silver staining gel were detected. Quantitative image analysis revealed that in total 47 protein spots showed significant changes in different genders of adult antennae. Thirty-five differentially expressed proteins were identified by Matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF) tandem mass spectrometer, among which 65.7% are involved in carbohydrate and energy metabolism, antioxidant system, transport, and amino acid/nucleotide metabolism. Some proteins identified here have not been reported previously in insect antennae. Identified male-biased proteins included odorant-binding protein 4, pheromone-binding protein-related protein 2, odorant-binding protein 14, prophenoloxidase-I, acyl-CoA dehydrogenase, aldo-keto reductase-like, carbamoyl phosphate synthetase, etc. whereas some proteins are female biased, such as antennae-rich cytochrome P450, aldehyde dehydrogenase, and putative glutamine synthetase. Alterations in the levels of some proteins were further confirmed by real time polymerase chain reaction (RT-PCR). The proteomic resources displayed here are valuable for the discovery of proteins from H. parallela antennae.

Does Anterior Fat Pad Removal Reduce the Incidence of Atrial Fibrillation after CABG? A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Atrial fibrillation (AF) is a common complication after coronary artery bypass grafting (CABG). Several prospective randomized controlled trials (RCTs) have evaluated the effect of intact and removed anterior fat pads on the incidence of AF after CABG with conflicting results. We collected these RCTs and conducted a meta-analysis to determine whether anterior fat pad removal is effective in preventing the new onset of AF after CABG. METHODS AND RESULTS: Prospective RCTs were collected for analysis and the main outcomes include the occurrence of AF after CABG, total hospital stay, and major complications. Statistical analysis was conducted using RevMan 5.0.18 software (The Cochrane Collaboration), and pooled estimates of the effect were reported as risk ratios (RRs) or mean differences (MDs) with their 95% confidence intervals (CIs). The results of this meta-analysis indicate that anterior fat pad removal was not associated with a decreased risk of occurrence of AF after CABG (RR = 1.34, 95% CI: 0.88-2.03; P = 0.18), and it also did not increase the risk of major complications (RR = 1.05, 95% CI: 0.75-1.47; P = 0.79) or lengthen total hospital stay (MD = 0.06, 95% CI: -0.46 to 0.58; P = 0.83) compared with the control group. CONCLUSION: Anterior fat pad removal did not decrease the risk of the occurrence of AF after CABG despite its safety and convenience, and it should not be used to prevent new-onset AF after CABG unless new evidence is provided.

[Telmisartan reduces retina vessel endothelial cell apoptosis via upregulating retinal ACE2-Ang-(1-7)-Mas axis in spontaneous hypertensive rats].

OBJECTIVE: To investigate the effects of angiotensin II (Ang II) antagonist telmisartan on retina vessel endothelial cell apoptosis and its impact on the ACE2-Ang-(1-7)-Mas axis in spontaneous hypertensive rats (SHR). METHODS: Thirty-six SHR 16 week-old were randomly divided into 3 groups (n = 12 each): SHR, SHRT (telmisartan 10 mg · kg-1 · d-1 by gastric gavage) and SHRTA group (telmisartan 10 mg · kg-1 · d-1 by gastric gavage plus intravenous injection of A-779 0.5 mg · kg-1 · d-1), twelve WKY rats served as normotensive control group. Systolic blood pressure was measured at pre-treatment and 8 weeks later. After 8 weeks, rats were sacrificed, the expression of ACE2 and Mas in retina were analyzed by qRT-PCR, Western blot and Immunohistochemistry, the Ang-(1-7) concentration in serum was measured by ELISA. Specimens were obtained and stained by hematoxylin and eosin, and the morphology of retina vessel was observed. Apoptosis of vessel endothelial cells were determined by using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling method. RESULTS: The systolic blood pressure of SHR, SHRT and SHRTA groups at baseline were significantly higher than age-matched WKY group (all P < 0.01). Eight weeks later, the systolic blood pressure group was significantly lower in SHRT group than in the SHR group (P < 0.01), this effect was partly reversed in SHRTA group. The retinal ACE2 mRNA and protein expression was significantly lower in SHR group than in WKY and SHRT groups (P < 0.01), which was similar between SHRT group and SHRTA group (P > 0.05). The retinal Mas mRNA and protein expression were significantly lower in SHR group compared to WKY and SHRT groups (all P < 0.01), which was significantly lower in SHRTA group than in the SHRT group (P < 0.05). ELISA results showed that serum Ang-(1-7) protein level was significantly lower in SHR group than in WKY group and SHRT group (both P < 0.05), which was lower in SHRTA group compared to SHRT group. Retinal vessel endothelial cell apoptosis was higher in SHR group than in WKY group, which could be reduced by cotreatment with telmisartan and this beneficial effect could be reversed by A-779. CONCLUSION: Telmisartan can reduce retinal vessel endothelial cell apoptosis via upregulating the ACE2-Ang-(1-7)-Mas axis.

[Application of Mimics three-dimensional imaging in percutaneous left atrial appendage closure with Watchman system].

OBJECTIVE: The three-dimensional (3D) structure of left atrial appendage (LAA) in atrial fibrillation patients were reconstructed by Mimics 3D imaging system, aiming at guiding for selection of both the size and location of the closure devices and making preliminary risk assessment of LAA closure with Watchman system. METHODS: Inclusion criteria were: ten voluntary patients with both atrial fibrillation and indication for LAA closure aging from 40 to 85 years old with contraindication for oral anticoagulants or unwillingness to take long-term oral anticoagulation therapy from May to December 2014. 3D reconstruction of LAA was preoperatively made by Mimics 3D imaging system. With the Mimics 3D reconstruction model and the results of both transesophageal echocardiography (TEE) and LAA radiography, the size and location for the closure device were chosen. The devices were planted at the ostium of the LAA. RESULTS: Ten atrial fibrillation patients were enrolled (average age: (66.3±11.9) years old) and all successfully implanted with the Watchman LAA closure devices. Nine of them were with non-valvular atrial fibrillation with average CHADS2-VAS score (3.2±1.7) and HAS-BLED score (2.7±1.6). The rest one was a valvular atrial fibrillation patient with the history of the percutaneous balloon mitral valvuloplasty (PBMV) without surgical indications of mitral valve replacement (MVR). There was no blood leakage around the device by regular postoperative TEE and LAA radiography examinations. There were no complications of bleeding, embolism, or stroke through both at peri-operative period and at 1 month follow-up post procedure. CONCLUSION: Preoperative Mimics 3D reconstruction of LAA by Mimics 3D imaging system among atrial fibrillation patients provides essential information guiding the successful LAA closures.

Association of glucose transporter 4 genetic polymorphisms with obstructive sleep apnea syndrome in Han Chinese general population: a cross-section study.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is strongly associated with the increasing prevalence of cerebrovascular events and metabolic syndrome. A growing number of studies have shown OSAS is an independent factor for insulin resistance, glucose intolerance and type2 diabetes. However, relationship of OSAS with dysglycemia is complex and still remains poorly understood. Glucose transporter 4 (GLUT4) gene is Human and rodents' main glucose transporter sensitive to insulin, and therefore confirmation of candidate gene polymorphisms and association with OSAS is needed. Aim of our study was to assess whether GLUT4 gene polymorphisms are associated with OSAS. METHODS: Patients hospitalized at People's Hospital of Xinjiang were selected from January to December 2010. A total of 568 Han subjects who possibly exist OSAS base on a history and physical examination were completed the polysomnography, 412of whom (72.5%) were diagnosed with OSAS, and 156 individuals were confirmed without OSAS (27.5%). 96 severe OSAS patients chosen from OSAS were used for DNA sequencing in functional domain. Blood samples were collected from all subjects and genotyping was performed on DNA extracted from blood cells. RESULTS: We performed GLUT4 genome sequencing, found 4 mutated sites. And finally selected three mutated sites such as rs5415, rs4517 and rs5435, according to principle of linkage disequilibrium (r2 > 0.8) and minimum gene allele frequency > 5%. All SNPs satisfied HEW (P > 0.05). Our study demonstrated a significant association of GLUT4 SNPrs5417 allele with OSAS, compared with controls (P < 0.05). Haplotype H1 (TCC) and H3 (CCC) defined as SNPrs5415, rs4517 and rs5435 are marginally associated with OSAS (P < 0.05). Frequencies of C haplotype of rs5417 in OSAS were higher than in controls. After adjustment for confounding factors, (AC + AA) genotype significantly reduces prevalence of OSAS, compared with CC genotype. Level of awake blood oxygen and lowest blood oxygen of (AA + AC) genotype was significantly superior to those of CC genotype. CONCLUSIONS: Our study demonstrates GLUT4 gene SNPrs5417 is associated with OSAS in hypertensive population. Carriers of AA + AC have less prevalence of obstructive sleep apnea syndrome than that of CC carriers.

[Association of SOCS3 gene polymorphisms with insulin resistance in Xinjiang Uygur population].

OBJECTIVE: To assess the association of suppressor of cytokine signaling 3 (SOCS3) gene polymorphisms with insulin resistance (IR) in Xinjiang Uygur population. METHODS: A cross-sectional study on metabolic diseases, e.g., obesity, was conducted on ethnic Uygurs in Hetian, Xinjiang of China. A total of 1292 Uygur individuals were enrolled. The sample size for IR subjects [homeostasis model assessment for insulin resistance (HOMA-IR) ≥ 2.96] was 323, whereas that for non-IR controls was 969 (HOMA-IR < 2.96). Representative variations were selected from database and genotyped with TaqMan polymerase chain reaction method. For the relatively isolated population from a homogeneous environment, a case-control study was conducted to assess the association between variations of SOCS3 gene and IR. RESULTS: A significant difference in genotype distribution of rs4969168 was detected between IR and control groups in males (chi square =7.216, P=0.027). Although the IR-related quantitative phenotypes did not significantly differ between individuals with GG, AG and AA genotypes of rs4969168 in the overall, male and female population (P > 0.05), the mean of body mass index and the median of fasting insulin increased in individuals with GG, AG, AA genotypes in males. Haplotype 2 (rs12953258C-rs4969168A-rs9914220C) was significantly associated with a higher prevalence of IR in males (P=0.023). Logistic regression analysis indicated that AG genotype of rs4969168 variation is a protective factor for IR in males (OR=1.772, 95% confidence interval: 1.081-2.906, P=0.023). CONCLUSION: Our study suggested that the rs4969168 polymorphism of SOCS3 gene is associated with IR in ethnic Uygur population from Xinjiang, China.

[Association of GIRK4 gene polymorphisms with essential hypertension in obese ethnics Uygur from southern Xinjiang].

OBJECTIVE: To assess the association of polymorphisms of G protein-coupled inwardly-rectifying potassium channels 4 (GIRK4) gene with essential hypertension in ethnic Uygurs from southern Xinjiang. METHODS: A total of 1194 (461 males and 733 females) Uygur residents aged 30 to 70 and with a body mass index (BMI) over 18.5 kg/m(2) were selected from Hetian region. All of the subjects have received questionnaire survey, physical examination, biochemical analysis and blood pressure measurement. They were divided into hypertensive group and normotensive group. Genotyping by the TaqMan polymerase chain reaction method was performed for 4 common single nucleotide polymorphisms (rs4937391, rs2604204, rs6590357 and rs1122149), and a case-control study was carried out. RESULTS: Genotype distributions of rs4937391, rs2604204, rs6590357 and rs1122149 in both groups were in Hardy-Weinberg equilibrium (P> 0.05). The average systolic blood pressure of CC genotype of rs11221497 single nucleotide polymorphism (SNP)[(132.69± 26.9) mmHg)] was higher than the CG genotype [(127.4± 22.7) mmHg] and GG genotype [(121.1± 26.3) mmHg]. There has a significantly difference in average systolic and diastolic blood pressures between CC and GG genotypes (P< 0.05). A case-control association analysis revealed that the rs11221497 SNP was in association with essential hypertension with the dominant model [P< 0.05, OR= 0.67 (0.49-0.93)]. Haplotype analysis indicated that H6(C-G-C-G) was significantly more common in normotensive group than hypertensive group (P= 0.001). CONCLUSION: The rs11221497 SNP of the GIRK4 gene is associated with essential hypertension in ethnic Uygur population in Xinjiang.

miR-130b-3p involved in the pathogenesis of age-related hearing loss via targeting PPARγ and autophagy.

The study focuses on the underlying regulatory mechanism of age-related hearing loss (ARHL), which results from autophagy dysregulation mediated by miR-130b-3p targeting PPARγ. We constructed miR-130b-3p knockout (antagomir) and PPARγ over-expression (OE-PPARγ) mice model by injecting mmu-miR-130b-3p antagomir and HBAAV2/Anc80-m-Pparg-T2A-mCHerry into the right ear' round window of each mouse, respectively. In vitro, we introduced oxidative stress within HEI-OC1 cells by H2O2 and exogenously changed the miR-130b-3p and PPARγ levels. MiRNA level was detected by RT-qPCR, proteins by western blotting and immunohistochemistry. Morphology of autophagosomes was observed by electron microscopy. In vivo, the cochlea of aged mice showed higher miR-130b-3p expression and lower PPARγ expression, while exogenous inhibition of miR-130b-3p up-regulated PPARγ expression. Autophagy-related biomarkers expression (ATG5, Beclin-1 and LC3B II/I) decreased in aged mice, which reversely increased after the inhibition of miR-130b-3p. The elevation of PPARγ demonstrated similar effects. Contrarily, exogenous overexpression of miR-130b-3p resulted in the decrease of ATG5, Beclin-1 and LC3B II/I. We created oxidative stress within HEI-OC1 by H2O2, subsequently observed the formation of autophagosomes under electron microscope, so as the elevated cell apoptosis rate and weakened cell viability. MiR-130b-3p/PPARγ contributed to the premature senescence of these H2O2-induced HEI-OC1 cells. MiR-130b-3p regulated HEI-OC1 cell growth by targeting PPARγ, thus leading to ARHL.

Effect of Jianpi therapy in treatment of chronic obstructive pulmonary disease: a systematic review.

OBJECTIVE: To evaluate the efficacy of Jianpi therapy in Traditional Chinese Medicine (TCM) for treatment of chronic obstructive pulmonary disease (COPD) in stable phase by performing a systematic review and meta-analysis. METHODS: The literatures concerning randomized controlled trials (RCTs) and quasi-RCTs comparing TCM treatment plus Western Medicine (WM) treatment with TCM alone, or TCM treatment vs no treatment, placebo for stable phase of COPD were searched in PubMed (1990-December 2010), in English and using Chinese National Knowledge Infrastructure (CNKI, 1990-December 2010), Chinese Biomedical Database (1990-December 2010), Wangfang Database (1990-December 2010), and Weipu (VIP) Database in Chinese. The quality assessment and data extraction for RCTs were conducted by two reviewers independently. Jadad scale and allocation concealment were used to assess the quality of the included studies, and meta-analyses were conducted with the Collaboration's Revman 5.0 software. RESULTS: Seventeen RCTs or quasi-RCTs involving 1269 patients were included. The methodological quality was poor in all trials except one trial (Jadad score = 4). In the meta-analysis, TCM-WM treatment was significantly superior to WM treatment in cure rate [OR = 3.82, 95% CI (2.45, 5.95)], and the effective rate between TCM treatment and placebo also had significant difference [OR = 4.31, 95% CI (2.35, 7.91)]. Moreover, pulmonary function of the patients in TCM-WM group and TCM group was significantly improved [forced vital capacity (FVC), P = 0.01, quality of life, P < 0.001]. CONCLUSION: The experience in TCM-WM treatment of COPD in stable phase was encouraging. The current evidence shows that TCM-WM treatment might be more efficient in effective rate, quality of life, and FVC than WM treatment alone. But for forced expiratory volume in one second (FEV1) and FEV1/FVC, no matter TCM-WM treatment compared with WM treatment alone or TCM treatment compared with placebo, there was no significant difference, with no obvious adverse reactions. Due to the low methodological quality of trials included, more RCTs of high quality in large scale are required.