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Polycystic ovary syndrome (PCOS) is a common disease caused by complex endocrine and metabolic abnormalities in women of childbearing age. Metformin is the most widely used oral hypoglycemic drug in clinic. In recent years, metformin has been used in the treatment of PCOS, but its mechanism is not clear. In this study, we aimed to investigate the effect of metformin on PCOS and its mechanism through PCOS mouse model. Female C57BL/6J mice aged 4-5 weeks were intragastrically given letrozole (1 mg/kg daily) combined with a high-fat diet (HFD) for 21 days to establish the PCOS model. After modeling, metformin (200 mg/kg daily) was intragastrically administered. One month later, the body weight and oral glucose tolerance test (OGTT) were measured. Hematoxylin eosin (H&E) staining was used to detect the pathological changes of ovary. The serum levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2 and testosterone (T) were measured by ELISA. The expression of DDX4/MVH was detected by immunohistochemistry. DDX4/MVH and PCNA were co-labeled by immunofluorescence. The protein levels of DDX4/MVH, PCNA, cyclin D2, AMPK and mTOR were detected by Western blot. The results showed that after metformin treatment, the body weights of PCOS mice were gradually returned to normal, glucose tolerance was significantly improved, serum E2 levels were increased, while AMH, LH, T levels and LH/FSH ratio were decreased. Ovarian polycystic lesions were reduced with reduced atresia follicles. Furthermore, the number of proliferative female germline stem cells (FGSCs) and levels of proliferation related proteins (PCNA, cyclin D2) were significantly increased, and the p-mTOR and p-AMPK levels were markedly up-regulated. These results suggest that metformin treatment not only improves hyperandrogenemia, glucose intolerance and polycystic ovarian lesions in PCOS, but also activates the function of FGSCs. The underlying mechanism may be related to the phosphorylation of AMPK and mTOR. These findings provide new evidence to use metformin in the treatment of PCOS and follicular development disorder.
Subject(s)
Animals , Female , Humans , Mice , AMP-Activated Protein Kinases , Cyclin D2 , Follicle Stimulating Hormone/therapeutic use , Luteinizing Hormone/therapeutic use , Metformin/pharmacology , Mice, Inbred C57BL , Oogonial Stem Cells/metabolism , Ovarian Cysts/drug therapy , Ovarian Neoplasms , Polycystic Ovary Syndrome/drug therapy , Proliferating Cell Nuclear Antigen/therapeutic use , TOR Serine-Threonine KinasesABSTRACT
@#AIM: To analyze the difference of macular retinal thickness between diabetic patients without apparent visual loss and normal subjects.<p>METHODS: Totally 40 cases(79 eyes)with type 2 diabetes without significant decrease of visual acuity(best corrected visual acuity, BCVA ≥0.8)in our hospital from April, 2018 to June, 2019 were enrolled as observation group and 64 cases(119 eyes)normal persons were enrolled as control group. The average retinal thickness in nine areas of macula, central retinal thickness(CRT), average retinal thickness(ART)and total volume(TV)of all patients were determined by optical coherence tomography(OCT), and the difference of average retinal thickness in nine areas of macula, CRT, ART and TV among them were compared.<p>RESULTS: The CRT, ART and TV(193.99±14.58μm, 291.07±12.24μm, 8.22±0.35mm3)in the observation group were significantly higher than those in the control group(187.38±12.24μm, 280.54±8.71μm, 7.92±0.25mm3), and the average retinal thickness in nine areas of macula in the observation group was significantly higher than that in the control group(<i>P</i><0.05).<p>CONCLUSION: Compared with normal persons, macular retinal thickness and TV are significantly thickened in early stage of type 2 diabetes.
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AIM:To analyze the cause of posterior capsular rupture in small incision non - phacoemulsification cataract surgery and investigate the treatment methods. METHODS: The clinical data of 108 cases ( 121 eyes ) undergone small incision non - phacoemulsification cataract surgery combined with intraocular lenses ( IOL) implantation were retrospectively analyzed. The causes of posterior capsular rupture and treatment of 6 patients (6 eyes) after surgery were analyzed and summarized. RESULTS: Six cases ( 6 eyes, 4. 96%) occurred posterior capsular rupture during the operation, of which 2 cases ( 2 eyes ) underwent posterior chamber IOL implantation intraoperative, 2 cases (2 eyes) receivedIIstage IOL implantation in the ciliary sulcus at 1wk postoperative, 2 cases ( 2 eyes ) were given anterior chamber IOL implantation. One case ( 1 eye ) whose vision acuity CONCLUSION:Posterior capsular rupture which occurs in different stages of the operation is the commonest intraoperative complication in small lincision non -phacoemulsification cataract surgery. With improving operative techniques, and continuously accumulating experience, incidence of posterior capsular rupture can be effectively reduced. Even posterior capsular rupture occurs intraoperative, patients can still get a good outcome after timely and proper treatment.
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·AlM: To investigate the distribution and related factors of corneal spherical aberration in the age-related cataract patients, and to provide a scientific basis for the application of aspheric intraocular lens ( lOL ) in cataract surgery patients. · METHODS: Retrospective study of 509 age -related cataract patients of 610 eyes in our hospital. Corneal spherical aberration, corneal curvature, corneal astigmatism and corneal Q -value were examined by iTrace visual function analysis. Statistical software SPSS16.0 was used to analyze statistically. · RESULTS: The range of corneal spherical aberration was 0 ~1.800μm. The mean coefficient of corneal spherical aberration was 0.266 ±0.010μm. Corneal spherical aberration was no significantly correlation with age, corneal curvature, corneal astigmatism ( r =0.71, 0.56, 0.93, P>0.05 ). There was positive correlation between corneal spherical aberration and Q-value ( r=0.086, P=0.03). · CONCLUSlON: Corneal spherical aberration varied greatly among age-related cataract patients.The choice of asphericity intraocular lens should be a matter of personal choice.
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In this study, we searched multiple databases for all relevant original articles (1996-2013). To investigate blood lead levels (BLL) and possible risk factors for lead exposure among children in China A total of 388 articles met our inclusion criteria. The overall geometric mean (GM) BLL was 71 µg/L, and the prevalence of elevated BLL (EBLL, defined as BLL ⋝ 100 µg/L) was 18.48% among children. The prevalence of EBLL remained significantly higher among boys. In children less than 6 years of age, there were significantly increasing trends in both BLL and prevalence of EBLL in an age-dependent manner. The ban on leaded gasoline significantly reduced the BLL as well as EBLL prevalence; however, children whose parents had lower educational levels or were exposed to lead in the workplace had a higher EBLL prevalence. Despite its decline over time, the average BLL among children in China remains higher than the average level most recently reported in the United States. Childhood lead poisoning remains a public health problem in China.
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Child , Child, Preschool , Female , Humans , Male , China , Environmental Exposure , Lead , Blood , Risk FactorsABSTRACT
Benzene is an established leukotoxin and leukemogen in humans. We have previously reported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to mediate the cellular response to DNA double strand break (DSB) caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026), as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phosphorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apoptosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.
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Benzene is an established leukotoxin and leukemogen in humans. We have previously reported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to mediate the cellular response to DNA double strand break (DSB) caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026), as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phosphorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apoptosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.
Subject(s)
Humans , Apoptosis , Physiology , Benzene , Toxicity , Catalysis , Chromones , Pharmacology , DNA Damage , Genetics , DNA Repair , Physiology , DNA-Activated Protein Kinase , Metabolism , K562 Cells , Morpholines , Pharmacology , Protein SubunitsABSTRACT
This study was aimed to investigate the inducing-apoptosis effect of arsenic trioxide (ATO) on imatinib (IM)-resistant chronic myeloid leukemia (CML) cell line KBM5R with T315I point mutation. CML cell line KBM5R with T315I point mutation and wild-type cell line KBM5 were selected for study. Resistance of KBM5R cells to IM and proliferation of KBM5 and KBM5R cells treated with ATO were detected by MTT; apoptosis of KBM5 and KBM5R cells were quantified by flow cytometry; the expression of apoptosis-related protein caspase-3, -8, -9 was determined by Western blot. The results showed that (1) IC(50) of KBM5R and KBM5 cells treated with IM were 12.66 ± 0.565 µmol/L and 0.303 ± 0.031 µmol/L respectively, and significantly different from each other. (2) the proliferation of KBM5 and KBM5R cells treated with different concentrations of ATO was inhibited in dose- and time-dependent manners at 24, 48, 72, 96 hours, and inhibition of KBM5R cell proliferation was stronger than KBM5 in the same drug concentration and time. (3) the apoptosis rate of KBM5 and KBM5R cells treated with 2, 4, 8 µmol/L ATO for 48 hours increased in a concentration-dependent manner, and the apoptosis rate of KBM5R was higher than that of KBM5 cells in the same drug concentration. (4) the expression of cleaved caspase-3, -8, -9 protein in KBM5 and KBM5R cells treated with 4 µmol/L ATO for 24 hours significantly increased. It is concluded that KBM5R cells are significantly resistant to IM; ATO can inhibit the proliferation and induce the apoptosis of KBM5R and KBM5 cells. As compared with wild-type KBM5 cells, effect of ATO on inhibition of proliferation and induction of apoptosis in KBM5R cells are more stronger. ATO can induce the apoptosis of KBM5 and KBM5R cells through the activation of apoptosis-related caspase-3, -8, -9 protein.
Subject(s)
Humans , Apoptosis , Arsenicals , Pharmacology , Benzamides , Caspase 3 , Metabolism , Caspase 8 , Metabolism , Caspase 9 , Metabolism , Cell Line, Tumor , Drug Resistance, Neoplasm , Genetics , Flow Cytometry , Imatinib Mesylate , Oxides , Pharmacology , Piperazines , Pharmacology , Point Mutation , Pyrimidines , PharmacologyABSTRACT
Objective To study the different expressions of receptor activator of nuclear factor-kappa B ligang(RANKL) mRNA in spleens of rats fed with diet of low calcium and high fluoride. Methods A 2× 2×2 factorial design was used and the factors were calcium, fluoride and action time. In the design, 40 Wistar rats [average body mass(118.9±13.5)g] were divided into four groups randomly by weight: control with normal diet (0.790%, calcium), low calcium group with low calcium intake(0.063%, calcium), high fluoride group with normal diet and high fluoride intake(100 mg/L, fluoride) and low calcium and high fluoride group with low calcium and high fluoride intake. After 4 and 8 months, 5 rats of each group were sacrificed and total RNA was extracted from spleen. And the expression levels of RANKL mRNA were determined by reverse transcription polymerase chain reaction (RT-PCR). Results At time of 4 months, the expression level of RANKL mRNA was 0.13± 0.05,0.13± 0.03,0.17±0.02,0.27± 0.05 and at time of 8 months, it was 0.11 ± 0.01,0.16 ± 0.02,0.16± 0.03,0.36 ± 0.07 in control group, low calcium group, high fluoride group, low calcium with high fluoride group, repectively. The factorial design AVONA showed that low calcium and high fluoride had significant effects on RANKL mRNA expression(F = 40.224,56.679, all P < 0.05) while action time had not(F = 2.850, P > 0.05 ). The interactions of low calcium with high fluoride or high fluoride with action time were signifieant(F = 7.247, 18.789, all P < 0.05) while the interaction of high fluoride with action time was not(F = 1.751, P > 0.05). Conclusions Low calcium alone or high fluoride alone or low calcium with high fluoride or low calcium with action time can increase the the RANKL mRNA expression level. High fluoride does not affect the RANKL mRNA level as the action time is prolonged.
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<p><b>OBJECTIVE</b>To evaluate the effect of the prognostic factors on long-term surgical outcome in myringoplasty.</p><p><b>METHODS</b>Retrospective cohort 205 patients (223 ears) with sandwich temporal fascia myringoplasty were analyzed using the multiple logistic regression analysis. The charts of inpatients had undergone myringoplasty before at least 2 years between January 1999 and November 2003 at Beijing Tongren Hospital. Postoperative follow-up rate was 78.2%. Their ages ranged from 12 to 65 years (mean = 34. 3 years). Their durations of disease ranged from 1 month to 25 years (mean = 16.07 months). The effect of prognostic factors on myringoplasty were investigated by variables noted from patients' files such as age, sex, causes of disease, duration of disease, period of dry ear of disease, operation types, places of tympanic membrane perforation, size of tympanic membrane perforation, status of middle ear and status of eardrum.</p><p><b>RESULTS</b>There were 11 ears with re-perforation of eardrum at the last follow-up. Successful closure of the tympanic membrane perforation was obtained in 95.1% of the ears (212 ears) with 2 to 5 years follow-up. There were 26 ears with other complications at the last follow-up. Operations were successful in 186 patients. The overall take rate of the myringoplasty was 83.4%. Multiple logistic regression analysis (ward) was subsequently carried out on these prognostic factors on overall take rate of the myringoplasty and yielded the following classification. Relative importance of the predictive variables was as follows: size of tympanic membrane perforation (OR = 1.900), duration of disease (OR = 1.003) and period of dry ear of disease (OR = 0.908). Hearing outcomes: the average air-bone gap improvement was 7.0 dB and the average air conduction improvement was 6.8 dB for all 175 myringoplasty procedures.</p><p><b>CONCLUSIONS</b>A long term follow-up was important. Late atelectatic pocket was a late complication and a cause of failure. A relatively smaller tympanic membrane perforation, a relatively shorter duration of disease and a relatively longer period of dry ear of disease were found to be significant prognostic factors positively influencing the success rate of myringoplasty.</p>
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult , Myringoplasty , Methods , Prognosis , Retrospective Studies , Treatment Outcome , Tympanic Membrane Perforation , General SurgeryABSTRACT
In this paper, some familiar algorithms of edge detection in ultrasound B-scan images are analyzed and studied. The results show that Sobel, Prewitt and Laplacian operators are sensitive to noise, Hough transform adapts to the whole detection, while LoG algorithm's average is zero and it couldn't change the whole dynamic area. Accordingly LoG algorithm is preferable.
Subject(s)
Humans , Algorithms , Artifacts , Image Enhancement , Methods , Pattern Recognition, Automated , Methods , Ultrasonography , MethodsABSTRACT
<p><b>OBJECTIVE</b>To study the genetic association of apolipoprotein (apo) E and apoCI gene polymorphisms with coronary heart disease (CHD) in China.</p><p><b>METHODS</b>apoE genotypes were identified by multiplex amplification refractory mutation system (multi-ARMS) and the apoCI promoter polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 186 cases with CHD (age: 65.0 +/- 10.5 years) and 350 controls (age: 63.6 +/- 8.3 years). The haplotype frequencies were estimated.</p><p><b>RESULTS</b>The frequencies of apoE E4/3 genotype (26.9%) and epsilon4 (14.5%) in CHD group were significantly higher than that in the control group (12.6%, 7.0%), P <0.05. The significant difference was also found for the apoCI locus and the CHD group showed higher rate of both for the H2 allele and genotypes, carrying this allele. Estimation of the haplotype frequencies indicated that the association between the apoE-CI haplotype and CHD was significantly strong. The apoE-epsilon4/apoCI-H2 was estimated to be responsible for 9.86% of CHD.</p><p><b>CONCLUSION</b>When the subjects carrying both epsilon4 and H2 alleles, they would have higher risk of suffering from CHD than controls.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Alleles , Apolipoproteins C , Genetics , Apolipoproteins E , Genetics , China , Epidemiology , Coronary Disease , Blood , Epidemiology , Genetics , Genotype , Haplotypes , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Risk FactorsABSTRACT
<p><b>OBJECTIVE</b>To evaluate relationship between ApoE gene polymorphism and coronary heart disease (CHD).</p><p><b>METHODS</b>Meta-analysis was applied with a random-effect model for the collected data.</p><p><b>RESULTS</b>Difference in pooled frequencies, d, of apoE genotypes E3/2, E4/2, E3/3, E4/3 and E4/4 between case and control groups were 2.3%, -0.8%, -8.5%, 10.5% and 0.9%, respectively. Difference in pooled frequencies, d, of apoE alleles epsilon2, epsilon3 and epsilon4 were -1.5%, -4.2% and 5.8%, respectively, with a statistical significance between four groups.</p><p><b>CONCLUSIONS</b>apoE gene polymorphism was involved in coronary heart disease. Persons with apoE E3/3 genotype or epsilon3 allele were not susceptible to CHD, but those with apoE E4/4 genotype or epsilon4 allele had higher risk suffering from CHD than others.</p>