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Metabolic engineering has been widely used for production of natural medicinal molecules. However, engineering high-yield platforms is hindered in large part by limited knowledge of complex regulatory machinery of metabolic network. N6-Methyladenosine (m6A) modification of RNA plays critical roles in regulation of gene expression. Herein, we identify 1470 putatively m6A peaks within 1151 genes from the haploid Saccharomyces cerevisiae strain. Among them, the transcript levels of 94 genes falling into the pathways which are frequently optimized for chemical production, are remarkably altered upon overexpression of IME4 (the yeast m6A methyltransferase). In particular, IME4 overexpression elevates the mRNA levels of the methylated genes in the glycolysis, acetyl-CoA synthesis and shikimate/aromatic amino acid synthesis modules. Furthermore, ACS1 and ADH2, two key genes responsible for acetyl-CoA synthesis, are induced by IME4 overexpression in a transcription factor-mediated manner. Finally, we show IME4 overexpression can significantly increase the titers of isoprenoids and aromatic compounds. Manipulation of m6A therefore adds a new layer of metabolic regulatory machinery and may be broadly used in bioproduction of various medicinal molecules of terpenoid and phenol classes.
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【Objective】 M3 muscarinic acetylcholine receptor(M3 receptor), encoded by CHRM3 gene, is widely distributed in the cardiovascular system and plays an important role in cardiac regulation. The aim of this study was to assess the association of genetic variants in M3 receptor with blood pressure(BP) responses to controlled dietary sodium and potassium interventions. 【Methods】 A total of 333 subjects from 124 families were recruited from the rural areas of northern China. After a three-day baseline observation, they were sequentially on a seven-day low-salt diet, a seven-day high-salt diet, and a seven-day high-salt diet plus potassium supplementation. Thirteen CHRM3 single nucleotide polymorphisms(SNPs) were selected for analysis. 【Results】 SNP rs10802811 of the CHRM3 was significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to both low-salt and high-salt diets while SNPs rs6429147, rs373288072, rs114677844 and rs663148 showed significant associations with systolic BP(SBP) and MAP responses to high-salt diet. In addition, SNP rs6692904 was significantly associated with SBP, DBP and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in M3 receptor are significantly associated with BP responses to sodium and potassium intervention, suggesting that M3 receptor may be mechanistically involved in BP salt and potassium sensitivity.
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【Objective】 Based on our previously established salt-sensitive hypertension cohort, we aimed to examine the association of genetic variants in uromodulin with blood pressure(BP) responses to dietary interventions of sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Mei County, Shaanxi Province, were recruited to establish the salt-sensitive hypertension study cohort. Among them, 333 non-parent subjects were selected and sequentially maintained on a normal-diet for 3 days, low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Thirteen single nucleotide polymorphisms(SNPs) in the uromodulin gene were genotyped on the MassARRAY platform. 【Results】 BP levels decreased from the baseline to low-salt diet, increased from low-salt to high-salt diet, and decreased again from the high-salt diet to the high-salt plus potassium supplementation intervention. SNPs rs77875418 and rs4997081 of the uromodulin gene were significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to high-salt diet. In addition, SNPs rs77875418, rs79245268, rs4293393, rs6497476, rs4997081, rs13333226, and rs12917707 were significantly associated with systolic BP(SBP), DBP, and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in uromodulin gene are significantly associated with BP responses to sodium and potassium supplementation, suggesting that uromodulin may be mechanistically involved in BP sodium-sensitivity and potassium-sensitivity.
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【Objective】 4-like protein with down-regulated expression and development in neural precursor cells (NEDD4L) plays an important role in blood pressure (BP) regulation and sodium homeostasis by regulating epithelial sodium channel protein. In this study, we aimed to explore the relationship of NEDD4L gene polymorphisms with BP responses to sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Meixian County, Shaanxi Province, were recruited to establish a salt-sensitive hypertension study cohort. All the subjects received a 3-day baseline survey, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Their BP was measured and peripheral blood samples were collected at different intervention periods. The 14 gene polymorphisms of NEDD4L gene were genotyped and analyzed by MassARRAY platform. 【Results】 BP decreased on a low-salt diet, and significantly increased on a high-salt diet, and decreased again after potassium supplementation. NEDD4L SNPs rs74408486 were significantly associated with systolic BP, diastolic BP and mean arterial pressure responses to the low-salt diet. SNPs rs292449 and rs2288775 were significantly associated with pulse pressure response to the high-salt diet. In addition, SNPs rs563283 and rs292449 were significantly associated with diastolic BP, mean arterial pressure, and pulse pressure responses to high-salt and potassium supplementation diet. 【Conclusion】 NEDD4L gene polymorphisms were significantly associated with BP responses to sodium and potassium intake, suggesting that NEDD4L gene may be involved in the development of salt sensitivity and potassium sensitivity.
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【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.
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Objective:To investigate the association between body mass index (BMI) trajectories in children and adolescents and subclinical renal damage (SRD) in adulthood.Methods:4 623 participants aged 6-18 years old were recruited from the ongoing cohort of Hanzhong adolescent hypertension study in 1987, and the subjects were followed up in 1989, 1992, 1995, 2005, 2013 and 2017, respectively. Group-based trajectory modeling was used to identify distinct BMI trajectories in longitudinal analysis. Generalized linear model was applied to examine the association between different BMI trajectories and SRD incidence in adulthood.Results:A total of 2 678 subjects from childhood to adulthood were enrolled in this study. All subjects were divided into three groups according to three distinct BMI trajectories: low-increasing BMI group ( n=1 017), moderate-increasing BMI group ( n=1 353), and high-increasing BMI group ( n=308). Over follow up for 30 years, a total of 248 participants (9.3%) developed SRD. Urinary albumin-to-creatinine ratio (uACR) in low to high-increasing BMI group was 0.9(0.6, 1.4), 1.0(0.7, 1.7), 1.6(0.8, 3.2), respectively ( P trend<0.001), and estimated glomerular filtration rate was 98.5(87.6, 111.6) , 96.2(86.4, 109.7), 95.3 (87.5, 125.0) ml·min -1·(1.73 m 2) -1, respectively ( P trend=0.025). The generalized linear model analysis showed that uACR was increased linearly from low to high-increasing BMI group [ β=3.16(95% CI 1.02-5.31), Ptrend=0.004]. There was no correlation or linear trend between BMI trajectory and estimated glomerular filtration rate [ β=-2.30(95% CI-5.18-0.57), Ptrend=0.117]. Compared with the low-increasing BMI group, the high-increasing BMI group had greater odds of experiencing SRD in adulthood after adjusting for multiple confounders such as age, gender, medical history and lifestyle ( OR=2.83, 95% CI 1.84-4.36, Ptrend<0.001). Conclusions:Higher BMI trajectorie is correlated with higher level of uACR and risk of SRD in middle age. Identifying long-term BMI trajectorie from early age may assist in predicting individuals′ renal function in later life.
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Objective:To observe the variation rend of serum creatinine(SCr)and estimated glomerular filtration rate(eGFR)with aging, and to explore the warning range of SCr for screening low eGFR of the elderly.Methods:A retrospective cross-sectional study was performed in 10 3513 participants, including 14 221 in 18-29 years old, 29 763 in 30-39 years old, 23 151 in 40-49 years old, 18 838 in 50-59 years old, 10 019 in 60-69 years old, 5 009 in 70-79 years old, 2 512 aged ≥80 years old.We adopted CKD-EPI formula based on Chronic Kidney Disease Epidemiology Collaboration(CKD-EPISCR)formula recommended by the Global Organization for Improving Outcomes in Kidney Disease 2012 to calculate eGFR.The SCr and eGFR levels were calculated according to age to show the trend of these with aging.Further, we used percentage to investigate the distribution of eGFR in population with normal SCr, and the percentile method to establish the warning range of SCr in the older adults.Results:With aging, SCr level showed an elevating trend in women( F=340.80, P<0.001), and gradually increased in men older than 50 years( F=111.05, P<0.001)and eGFR declined with increasing age( F=8 301.60, 9 114.53, P<0.001). In population with normal SCr, the proportions of eGFR<60 and 60-75 ml·min -1·1.73m -2 were 3.83%(661/17 280)and 12.50%(2 160/17 280)in older adults aged 60-74 years respectively, but were 10.39%(488/4 699)and 22.75%(1 069/4 699)in old-older adults aged 75 years and over respectively, and were 0.07%(56/84 145)and 0.91%(762/84 145)in younger adults below 60 years old respectively.In the same distribution of eGFR, SCr levels of older adults aged 60-74 years and old-older adults aged 75 years and over were lower than that of younger population( P<0.001). In old-older adults aged 75 years and over, the warning range of SCr was 98.76-126.03 μmol/L for men and 95.12-130.00 μmol/L for women in individuals with 45 ≤ eGFR<60 ml·min -1·1.73m -2. Conclusions:The SCr level of older adults is lower than younger individuals in same distribution of eGFR.SCr level is still in the reference range in some of older individuals with eGFR-confirmed renal function impairment.The warning range of SCr is needed, especially in older adults, so as to provide reference for the rational use of medicine and disease management.
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Primary liver cancer is the fourth most common malignant tumor and the second leading cause of tumor death in China. The development of novel biomarkers for early diagnosis and treatment of liver cancer patients is important to improve the survival rate. The most common tumor biomarkers in clinical practice are glycoproteins currently. With omics technologies, the clinically significant glycoproteomics and glycomics for liver cancer diagnosis are discovered. In this article, a variety of glycobiomarkers were summarized. Methods, problems and challenges for clinical detection are posed. The relevant techniques of glycoprotein research, including high-throughput omics method and single glycoprotein detection are discussed, as well as potential liver cancer glycoprotein markers based on these techniques. The potential application of the glycoproteins in the clinical diagnosis of liver cancer is also considered.
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Objective:To observe the clinical effects of intraperitoneal perfusion of bevacizumab combined with albumin paclitaxel and carboplatin in the treatment of malignant peritoneal adhesion caused by ovarian cancer.Methods:From January 2016 to December 2020, 54 patients treated in our hospital with malignant peritoneal adhesions caused by ovarian cancer were enrolled in this study. They were randomly divided into experimental group ( n=27) and control group ( n=27) according to the random number table method. The treatment regimen of the experimental group was intravenous infusion of albumin paclitaxel plus intraperitoneal infusion of carboplatin and bevacizumab. The treatment regimen of the control group was intra-venous infusion of albumin paclitaxel plus intraperitoneal infusion of carboplatin. The treatment was repeated every 21 days, and the therapeutic effect was evaluated every two cycles. The treatment lasted for six cycles. The efficacy and incidence of adverse reactions were compared between the two groups. Results:The remission rate of incomplete malignant bowel obstruction of the experimental group was higher than that of the control group [85.19% (23/27) vs. 59.26% (16/27)], the total effective rate of the experimental group was higher than that of the control group [74.07% (20/27) vs. 44.44% (12/27)], and there were statistically significant differences ( χ2=4.523, P=0.033; χ2=4.909, P=0.027). After treatment, the levels of vascular endothelial growth factor (VEGF) in ascites of the experimental group and the control group were significantly lower than those before treatment [(80.33±1.41) pg/ml vs. (310.45±3.35) pg/ml, t=449.884, P<0.001; (135.68±1.60) pg/ml vs. (310.46±3.09) pg/ml, t=499.281, P<0.001], and after treatment, the VEGF level in the experimental group decreased more significantly than that in the control group ( t=-134.907, P<0.001). Patients in the experimental group and the control group tolerated the treatment well, and there were no significant differences in the incidences of adverse reactions such as hypertension (11.11% vs. 3.70%, χ2=0.270, P=0.603), neutropenia (14.81% vs. 11.11%, χ2<0.001, P>0.999), peripheral neuropathy (3.70% vs. 0, χ2<0.001, P>0.999), diarrhea (7.41% vs. 3.70%, χ2<0.001, P>0.999), nausea (3.70% vs. 0, χ2<0.001, P>0.999), epistaxis (7.41% vs. 0, χ2=0.519, P=0.471) or albuminuria (3.70% vs. 0, χ2<0.001, P>0.999) between the two groups. Conclusion:Intraperitoneal perfusion of bevacizumab combined with chemotherapy is superior to simple chemotherapy in the treatment of malignant peritoneal adhesion caused by ovarian cancer.
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Plant-derived labdane-related diterpenoids (LRDs) represent a large group of terpenoids. LRDs possess either a labdane-type bicyclic core structure or more complex ring systems derived from labdane-type skeletons, such as abietane, pimarane, kaurane, etc. Due to their various pharmaceutical activities and unique properties, many of LRDs have been widely used in pharmaceutical, food and perfume industries. Biosynthesis of various LRDs has been extensively studied, leading to characterization of a large number of new biosynthetic enzymes. The biosynthetic pathways of important LRDs and the relevant enzymes (especially diterpene synthases and cytochrome P450 enzymes) were summarized in this review.
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Traditional Chinese medicine(TCM) is an important feature of cancer treatment in China. The methods to tap the advantages of TCM, reasonably evaluate and accurately apply Chinese patent medicines have become current research hotspots and difficulties. TCM takes syndrome differentiation and treatment as the core, with the characteristics of overall regulation and multi-targets efficacy. Therefore, the post-marketing survival benefit evaluation of Chinese patent medicines for cancer is different from that in modern medicine. The primary treatment goals in cancer patients include to improve the disease control rate and prolong their survival time. At present, Chinese patent medicines for cancer patients are lacking indepth studies on survival benefit at the post-marketing stage. In addition, the characteristics of individualized treatment with TCM have also increased the complexity of clinical research on TCM. Therefore, it is of certain practical significance and necessity to evaluate the survival benefit of Chinese patent medicines for cancer after marketing. Based on this, in this paper, we first summarized the technical methodological means of survival benefit evaluation at this stage, and then explored the post-marketing survival benefit evaluation of Chinese patent medicines for cancer from three aspects: the evaluation of cancer treatment effect based on survival time and quality of life, treatment-related toxicity and the auxiliary effect of TCM, and the improvement effect for tumor-related symptoms. Based on the practices of early clinical researches, and according to the insufficient efficacy evaluation of current clinical research on Chinese patent medicines, this paper proposed to improve the evaluation system for clinical researches on Chinese patent medicines, establish the evaluation method with TCM characteristics, clarify the dominant population, lay a theoretical foundation for the evaluation of post-marketing survival benefits of Chinese patent medicines for cancer in the future, and promote the modernization process of TCM.
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Humans , China , Drugs, Chinese Herbal/therapeutic use , Marketing , Medicine, Chinese Traditional , Neoplasms/drug therapy , Nonprescription Drugs/therapeutic use , Quality of LifeABSTRACT
Objective:To investigate the recovery of patients with acute thallium poisoning after 9 years.Methods:A group of 14 patients with familial thallium poisoning who were admitted to our hospital in 2010 were followed up for 9 years.Results:Among the 14 patients with acute thallium poisoning, one patient died on the 14th day after poisoning, and all the other survivors were followed up 9 years later. The general condition of all the patients was significantly better than that of poisoning 9 years ago. The alopecia of all cases disappeared, the newborn hair grew normally, without gastrointestinal symptoms, numbness, pain in the limbs and mental symptoms. All the patients returned to normal intelligence and physical strength and had a normal life. One patient (No. 5) gave birth to 2 children successively after discharge. The first child was 6 years old and the second child was 2 years old. Both growth and intelligence were not different from those of the same age. Currently, the third pregnancy was more than 7 months. No.6 and No.10 patients were poisoned in their teenage and were currently all studying in university. No.6 patient suffered from Hashimoto's thyroiditis 7 years after poisoning, and he has been taking thiamazole tablets for two years. Poisoned infants, No.7, 8 ,11 and 12, were school-age children with normal growth, mental development and excellent academic performance. Among the 13 surviving patients, blood and urine samples from No. 1, No. 3, and No. 4 patients were collected, and no thallium concentration was detected, and biochemical examina-tion and neurological examination were all normal.Conclusions:Patients with acute thallium poisoning have a favorable prognosis according to the follow-up after 9 years. All patients have no obvious sequelae and have normal labor ability. Young women have normal fertility, and children have normal growth and mental development.
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The aetiology of developmental dyslexia (DD) is complex; although candidate genes have been suggested, the molecular mechanism and risk factors remain unknown. The KIAA0319 gene is functionally related to neuronal migration and axon growth, and several studies have examined associations between KIAA0319 polymorphisms with DD, but the results remain inconsistent. The sample size affects the results of meta-analysis. The aim of this meta-analysis was to clarify the effect of KIAA0319 polymorphisms on dyslexia susceptibility according to the available evidence. All eligible case–control and transmission/disequilibrium test (TDT) studies published until March 2018 were identified by searchingMedline, PubMed, Embase, Web of Science and Chinese Biomedical Database, limited to Chinese and English language papers. Pooled odds ratios and 95% confidence intervals were calculated using STATS package v12.0. A total of 11 related studies, including 3130 cases of dyslexia and 3460 healthy control subjects, as well as four TDT studies with 842 families were included in our meta-analysis. The results indicated that the polymorphisms rs4504469, rs2038137, rs2179515, rs3212236, rs6935076, rs9461045, rs2143340 and rs761100 have no association between the polymorphisms and dyslexia risk. Three subgroup meta-analyseswere performed according to the study design, country and population. The stratified analysis revealed that the KIAA0319 rs4504469 minor allele was a risk allele t in the TDT subgroup, rs3212236 minor allele was a risk allele t in the UK subgroup and rs6935076 minor allele was a risk allele t in the Canada subgroup. Further studies with larger sample sizes that assess gene–gene and gene–environment interactions are required. The sample size of our study is larger than that of the previous studies, and the results are different from those of the previous studies.We have synthesized all the current studies on KIAA0319 and obtained reliable results.
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<p><b>OBJECTIVE</b>To observe the effect of crocetin on autophagy in rat hepatocytes exposed to lipopolysaccharide (LPS) and D-galactosamine (D-gal) and explore the mechanism.</p><p><b>METHODS</b>Cultured rat hepatocytes were exposed to LPS (1 mg/L) and Dgal (60 mg/L) to induce cell injury and treated with crocetin, 3MA, or crocetin+3MA. Twelve hours after the treatments, the cells were examined for levels of ALT, AST and LDH in the supernatant using ELISA. LC3 fluorescence in the cells following immunofluorescence staining was observed using fluorescence microscopy. Autophagosomes in the cells were observed by transmission electron microscopy, and the cellular expressions of LC3, p62 and SIRT1 were detected using Western blotting.</p><p><b>RESULTS</b>The levels of ALT, AST and LDH in the hepatocytes were elevated after LPS- and D-gal-induced injury, reached the highest levels after 3MA treatment, but were decreased significantly by crocetin treatment. LC3 fluorescence increased obviously in the injured hepatoctyes, and the increment was the most obvious in crocetin-treated cells; LC3 fluorescence was decreased significantly after 3MA treatment. Cell injury induced obvious increase in autophagy in the hepatocytes, and the number of autophagosomes increased significantly after crocetin treatment but was reduced significantly after 3MA treatment. The cell injury caused an obvious up-regulation of LC3 and SIRT1 expression and down-regulated p62 expression. LC3 and SIRT1 expression levels were the highest and the expression of p62 was the lowest in cells with crocetin treatment. 3MA treatment significantly reduced the expression of LC3 and SIRT1 and increased the expression of p62 in the injured cells.</p><p><b>CONCLUSIONS</b>Autophagy is increased in injured rat hepatocytes, and crocetin can promote autophagy in the injured cells to reduce further cell injury.</p>
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Objective To investigate and compare the effects of jejunal interposition and Roux-en-Y surgery after total gastrectomy. Methods The clinical data of 41 patients with gastric cancer who underwent total gastrectomy in our hospital from June 2013 to June 2016 were retrospectively analyzed.According to the different ways of reconstruction of digestive tract,the patients were divided into observation group and control group.Patients of the observation group were with jejunal interposition surgery,while patients of the control group were trea-ted with Roux-en-Y surgery,and the effects of the two groups were compared and analyzed.Results There was no significant difference be-tween the two groups in the time of reconstruction,length of hospital stay and the incidence of complications(P>0.05).One year after sur-gery,incidence of complications,albumin,total health score,fatigue score,and disgust score of the observation group were significantly better than those of the control group with statistically significant difference(P<0.05).There was no significant difference between the two groups in survival rate,hemoglobin,total protein,weight changes(P>0.05).Conclusion For patients with total gastrectomy,jejunal interposition and Roux-en-Y surgery had similar effect.But in terms of the long-term effect,jejunal interposition can reduce complications and improve lev-el of nutrition and quality of life.
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Objective To observe longitudinal changes in the intraocular pressure (IOP),the cornea and iris blood vessels in normal rats with bulb external scleral explants.Methods Totally 18 normal rats were enrolled in the experiment.Conjunctival incisions of the right eyes of these rats were performed,followed by the placement of a balloon catheter under the lateral rectus muscle and inflation at 4-5 ATM.The IOP was measured and iris images were taken longitudinally before and after pressuring and pressure withdrawing respectively.Results IOP was elevated to (40.66 ± 10.55) mm-Hg (1 kPa =7.5 mmHg) immediately after pressing,which was over the baseline (8.45 ± 1.23)mmHg (P=0.000),and then decreased gradually at 15 min,30 min,45min,60 min after pressing,but the IOPs were still greater than the baseline.There were significant differences in IOPs at 15 min,30 min,45 min after pressing and the baseline (all P ＜ 0.05),while no difference in this variable at 60 min after pressing and the baseline (P =0.929).However,the IOP was quickly reduced to (6.09 ± 0.49) mmHg at once after pressure withdrawing,which was below the baseline (P =0.000),and then gradually returned to the baseline at 15 min,30 min after pressure withdrawing.The corneal edema and dilation of iris vessels were observed after pressuring,and following corneal winkle and dilated iris vessels after pressure withdrawing.Conclusion Bulb external scleral explant can result in elevated IOP immediately,then decreased gradually.With the increase of compressing,the IOP of the contralateral eye tends to increase.Bulb external scleral explant may affect uveoscleral outflow pathway of aqueous humor in rats.
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Objective To analyze miR-10b expression level and the gene upstream methylation level in schwannomas so as to explore and identify the potential target genes for miR-10b in schwannomas .Methods The miR-10b with its potential target genes including HOXB 3 ,HOXD10 ,PTEN ,PIK3CA ,MAPRE1 and HADC4 were quantitatively analyzed by PCR in 13 cases of schwannomas and 6 cases of human vestibulocochlear nerves . We studied the correlation between the differentially expressed genes and the clinical characteristics of schwannomas . Finally ,the differences in miR-10b gene upstream methylation levels were measured and analyzed by pyrosequencing between schwannomas and normal vestibulocochlear nerves .Results Compared with that of normal nerves ,the expression level of miR-10b was significantly higher (P=0 .0003) while the level of PTEN was lower (P=0 .0047) in schwannomas .Negative correlation existed between the levels of miR-10b and PTEN (P=0 .001 , r= -0 .689) . Moreover ,the methylation level of the miR-10b gene promoter was downregulated in schwannomas ;it had negative correlation with the expression level of miR-10b (P= 0 .011 , r= -0 .571) .There was a significant difference in tumor mass diameter between miR-10b higher expression group and lower group (P=0 .016);however ,there was no difference in age or recurrence rate (P>0 .05) .Conclusion The downregulation of methylation level of the promoter leads to higher expression of miR-10b gene ,and it may targetedly inhibit the expression of PTEN .
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Approximately 2,300 genes are found to be associated with spermiogenesis and their expressions play important roles in the regulation of spermiogenesis. In recent years, more and more attention has been focused on the studies of the genes associated with oligospermia, asthenospermia and teratospermia and their molecular mechanisms. Some genes, such as GSTM1, DNMT3L, and CYP1A1, have been shown to be potentially associated with oligospermia; some, such as CATSPER1, CRISP2, SEPT4, TCTE3, TEKT4, and DNAH1, with asthenospermia; and still others, such as DPY19L2 and AURKC, with teratospermia. These findings have provided a molecular basis for the studies of the pathogenesis of oligospermia, asthenospermia and teratospermia, as well as a new approach to the exploration of new diagnostic and therapeutic techniques.
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Humans , Male , Asthenozoospermia , Genetics , Aurora Kinase C , Genetics , Calcium Channels , Genetics , Cytochrome P-450 CYP1A1 , Genetics , Cytoplasmic Dyneins , DNA (Cytosine-5-)-Methyltransferases , Genetics , Dyneins , Genetics , Glutathione Transferase , Genetics , Glycoproteins , Genetics , Membrane Proteins , Genetics , Microtubule Proteins , Genetics , Oligospermia , Genetics , Spermatogenesis , Genetics , Teratozoospermia , GeneticsABSTRACT
<p><b>BACKGROUND</b>There are ON- and OFF-pathways in the normal vertebrate retina. Short- and long-flash electroretinogram (ERG) are suitable methods to observe the function of ON- and OFF-pathways in vivo, respectively. It is clear that high intraocular pressure (IOP) might cause dysfunction of cone-dominated photopic negative response (PhNR) in monkeys with high IOP in ON-pathway. However, whether cone-dominated OFF-responses are also affected is less known. The aim of this study was to observe photopic OFF-responses of ERG in monkeys with high IOP.</p><p><b>METHODS</b>Nine monkeys were involved in the experiment from January 2006 to December 2016. High IOP was induced in the right eye by laser coagulation of the mid-trabecular meshwork in five monkeys. Six years after the laser coagulation, both short- and long-flash of the photopic ERG were recorded. Stimulus light was red flashes superimposed on a blue background. Four normal monkeys were examined under the same ERG protocols as controls. Paired t- test was used to compare the difference of each ERG parameter between the lasered eye and the fellow eye. Analysis of variance (ANOVA) with Tukey adjustment was adopted to calculate the differences among the lasered eye, the fellow eye, and the eyes of normal monkeys.</p><p><b>RESULTS</b>The mean amplitude of a-wave (11.73 ± 2.05) and PhNR (8.67 ± 2.44) in lasered eyes was significantly lower than that of a-wave (21.47 ± 3.15) and PhNR (22.05 ± 3.42) in fellow eyes (P = 0.03 and P = 0.01, respectively) in response to short flash. The mean amplitude of d-wave (1.60 ± 0.59) and i-wave (3.13 ± 0.64) was significantly reduced in the lasered eyes than that of d-wave (4.01 ± 0.56) and i-wave (8.79 ± 1.75) in the fellow eyes (P = 0.02 and P = 0.02, respectively) in response to long flash.</p><p><b>CONCLUSIONS</b>Reduced OFF-responses are recorded in monkeys with high IOP when dysfunction of photoreceptor is involved. The reduced OFF-responses to long-flash stimulus show evidence of anomalous retinal circuitry in glaucomatous retinopathy.</p>
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Objective To discuss the quality of life in the postoperative patients with aortic valve replacement (AVR) and related influencing factors .Methods The changes of preoperative and postoperative survival quality in 102 cases of AVR surgery were assessed by using the SF‐36 scale ,and the Logistic regression was used to analyze the impact of age ,effective valve orifice area and prosthetic valve on the quality of life .Results Five patients died during follow‐up .The relative baseline survey after postopera‐tive 1 year showed that the quality of life of patients was significantly improved ,the Logistic regression analysis revealed that a lar‐ger effective orifice area(EOA) and biological valve replacement could have higher health scale scores ,and showed a positive corre‐lation .Conclusion The quality of life in the postoperative patients with AVR is affected by the valve type and EOA of prosthetic valve .