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Objective:To study the methods of hormone-related teaching in standardized residency training of endocrinology.Methods:From February 2022 to June 2022, 25 residents in the Department of Endocrinology, Peking University Third Hospital were given a standardized residency training. The teaching mode combined with a hundred years of insulin development was adopted to practice insulin teaching, and questionnaires were evaluated before and after the teaching. Chi-square test was performed by SPSS 20.0.Results:A total of 31 physicians participated in the training, and 25 residents who were included in the first-stage standardized training were analyzed. Before the training, only 3 people (12%) knew the development history of insulin, and 10 people (40%) answered all the questions about clinical use of insulin correctly. After the training, 23 residents (92%) said they knew or were familiar with the history of insulin development, and 20 residents (80%) answered the questions about the clinical use of insulin correctly, all of which were higher than those before the training, and the difference was statistically significant.Conclusion:The integration of medical history in standardized residency training in endocrinology department can effectively improve the teaching effect, and enhance the humanity quality of young doctors, which can become an effective vehicle in standardized residency training.
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Objective:To observe the effects of overexpression of polypyrimidine tract binding protein-associated splicing factor (PSF) on the endoplasmic reticulum (ER) oxidative stress damage of human retinal microvascular endothelial cells (hRMEC) under high concentration of 4-hydroxynonenal (4-HNE).Methods:The logarithmic growth phase hRMEC cultured in vitro was divided into normal group, simple 4-HNE treatment group (simple 4-HNE group), empty plasmid combined with 4-HNE treatment group (Vec+4-HNE group), and PSF high expression combined with 4-HNE treatment group (PSF+4-HNE group). In 4-HNE group, Vec+4-HNE group, and PSF+4-HNE group cell culture medium, 10 μmol/L 4-HNE was added and stimulated for 12 hours. Subsequently, the Vec+4-HNE group and PSF+4-HNE group were transfected with transfection reagent liposome 2000 into pcDNA empty bodies and pcDNA-PSF eukaryotic expression plasmids, respectively, for 24 hours. Flow cytometry was used to detect the effects of 4-HNE and PSF on cell apoptosis. The effect of PSF overexpression on the expression of reactive oxygen species (ROS) in hRMEC was detected by 2', 7'-dichlorodihydrofluorescein double Acetate probe. Western blot was used to detect ER oxide protein 1 (Ero-1), protein disulfide isomerase (PDI), C/EBP homologous transcription factor (CHOP), glucose regulatory protein (GRP) 78, protein kinase R-like ER kinase (PERK)/phosphorylated PERK (p-PERK), and Eukaryotic initiation factor (eIF) 2α/the relative expression levels of phosphorylated eIF (peIF) and activated transcription factor 4 (ATF4) proteins in hRMEC of normal group, 4-HNE group, Vec+4-HNE group, and PSF+4-HNE group. Single factor analysis of variance was performed for inter group comparison.Results:The apoptosis rates of the simple 4-HNE group, Vec+4-HNE group, and PSF+4-HNE group were (22.50±0.58)%, (26.93±0.55)%, and (11.70±0.17)%, respectively. The intracellular ROS expression levels were 0.23±0.03, 1.60±0.06, and 0.50±0.06, respectively. The difference in cell apoptosis rate among the three groups was statistically significant ( F=24.531, P<0.05). The expression level of ROS in the Vec+4-HNE group was significantly higher than that in the simple 4-HNE group and the PSF+4-HNE group, with a statistically significant difference ( F=37.274, P<0.05). The relative expression levels of ER Ero-1 and PDI proteins in the normal group, simple 4-HNE group, Vec+4-HNE group, and PSF+4-HNE group were 1.25±0.03, 0.45±0.03, 0.63±0.03, 1.13±0.09, and 1.00±0.10, 0.27±0.10, 0.31±0.05, and 0.80±0.06, respectively. The relative expression levels of CHOP and GRP78 proteins were 0.55±0.06, 1.13±0.09, 0.90±0.06, 0.48±0.04 and 0.48±0.04, 1.25±0.03, 1.03±0.09, 0.50±0.06, respectively. The relative expression levels of Ero-1 ( F=43.164), PDI ( F=36.643), CHOP ( F=42.855), and GRP78 ( F=45.275) proteins in four groups were compared, and the differences were statistically significant ( P<0.05). Four groups of cells ER p-pERK/pERK ( F=35.755), peIF2 α/ The relative expression levels of eIF ( F=38.643) and ATF4 ( F=31.275) proteins were compared, and the differences were statistically significant ( P<0.05). Conclusion:PSF can inhibit cell apoptosis and ROS production induced by high concentration of 4-HNE, and its mechanism is closely related to restoring the homeostasis of ER and down-regulating the activation level of PERK/eIF2α/ATF4 pathway.
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Objective:To observe the effects of p21 activated kinase 4 (PAK4) on the mitochondrial function and biological behavior in retinal vascular endothelial cells.Methods:The experimental study was divided into two parts: in vivo animal experiment and in vitro cell experiment. In vivo animal experiments: 12 healthy C57BL/6J male mice were randomly divided into normal control group and diabetes group, with 6 mice in each group. Diabetes mice were induced by streptozotocin to establish diabetes model. Eight weeks after modeling, quantitative real-time polymerase chain reaction and Western blots were performed to detect the expression of PAK4 in diabetic retinas. In vitro cell experiments: the human retinal microvascular endothelial cells (hRMEC) were divided into three groups: conventional cultured cells group (N group), empty vector transfected (Vector group); pcDNA-PAK4 eukaryotic expression plasmid transfected group (PAK4 group). WB and qPCR were used to detect transfection efficiency, while scratching assay, cell scratch test was used to detect cell migration in hRMEC of each group. In vitro white blood cell adhesion experiment combined with 4 ', 6-diamino-2-phenylindole staining was used to detect the number of white blood cells adhering to hRMEC in each group. The Seahorse XFe96 cell energy metabolism analyzer measures intracellular mitochondrial basal respiration, adenosine triphosphate (ATP) production, maximum respiration, and reserve respiration capacity. The t-test was used for comparison between the two groups. Single factor analysis of variance was used for comparison among the three groups. Results:In vivo animal experiments: compared with normal control group, the relative expression levels of PAK4 mRNA and protein in retina of diabetic mice were significantly increased, with statistical significance ( t=25.372, 22.419, 25.372; P<0.05). In vitro cell experiment: compared with the N group and Vector group, the PAK4 protein, mRNA relative expression and cell mobility in the hRMEC of PAK4 group were significantly increased, with statistical significance ( F=36.821, 38.692, 29.421; P<0.05). Flow cytometry showed that the adhesion number of leukocytes on hRMEC in PAK4 group was significantly increased, and the difference was statistically significant ( F=39.649, P<0.01). Mitochondrial pressure measurement results showed that the capacity of mitochondrial basic respiration, ATP production, maximum respiration and reserve respiration in hRMEC in PAK4 group was significantly decreased, with statistical significance ( F=27.472, 22.315, 31.147, 27.472; P<0.05). Conclusion:Over-expression of PAK4 impairs mitochondrial function and significantly promotes leukocyte adhesion and migration in retinal vascular endothelial cells.
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Objective:To observe the effect of high expression of polypyrimidine tract-binding protein-associated splicing factor (PSF) on low concentration of 4-hydroxynonenal (4-HNE) induced human retinal microvascular endothelial cells (HRMECs), and explore the possible mechanism.Methods:The HRMECs cultured in vitro were divided into 4-HNE treated group, PSF overexpression group combined with 4-HNE group (PSF+4-HNE group), PSF overexpression+ML385 treatment combined with 4-HNE group (PSF+ML385+4-HNE group), and 4-HNE induced PSF overexpression group with LY294002 pretreatment (LY294002+4-HNE+PSF group). Cell culture medium containing 10 μmmol/L 4-HNE was added into 4-HNE treatment group, PSF+4-HNE group, PSF+ML385+4-HNE group for 12 hours to stimulate oxidative stress. 1.0 μg of pcDNA-PSF eukaryotic expression plasmid were transfected into PSF+4-HNE group and PSF+ML385+4-HNE group to achieve the overexpression of PSF. Also cells were pretreated with ML385 (5 μmol/L) for 48 hours in the PSF+ML385+4-HNE group, meanwhile within the LY294002+4-HNE+PSF group, after pretreatment with LY294002, cells were treated with plasmid transfection and 4-HNE induction. Transwell detects the migration ability of PSF to HRMECs. The effect of PSF on the lumen formation of HRMECs was detected by using Matrigel in vitro three-dimensional molding method. Flow cytometer was used to detect the effect of PSF overexpression on reactive oxygen (ROS) level in HRMECs. Protein immunoblotting was used to detect the relative expression of PSF, nuclear factor E2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1) protein, and phosphoserine threonine protein kinase (pAkt) protein. The comparison between the two groups was performed using a t-test. Results:The number of live cells, migrating cells, and intact lumen formation in the 4-HNE treatment group and the PSF+4-HNE group were 1.70±0.06, 0.80±0.13, 24.00±0.58, 10.00±0.67, and 725.00±5.77, 318.7±12.13, respectively. There were significant differences in the number of live cells, migrating cells, and intact lumen formation between the two groups ( t=12.311, 15.643, 17.346; P<0.001). The results of flow cytometry showed that the ROS levels in the 4-HNE treatment group, PSF+4-HNE group, and PSF+ML385+4-HNE group were 816.70±16.67, 416.70±15.44, and 783.30±17.41, respectively. There were statistically significant differences between the two groups ( t=16.311, 14.833, 18.442; P<0.001). Western blot analysis showed that the relative expression levels of pAkt, Nrf2, and HO-1 proteins in HRMECs in the 4-HNE treatment group, PSF+4-HNE group and LY294002+4-HNE+PSF group were 0.08±0.01, 0.57±0.04, 0.35±0.09, 0.17±0.03, 1.10±0.06, 0.08±0.11 and 0.80±0.14, 2.50±0.07, 0.50±0.05, respectively. Compared with the PSF+4-HNE group, the relative expression of pAkt, Nrf2, and HO-1 proteins in the LY294002+4-HNE+PSF group decreased significantly, with significant differences ( t=17.342, 16.813, 18.794; P<0.001). Conclusion:PSF upregulates the expression of HO-1 by activating the phosphatidylinositol 3 kinase/Akt pathway and inhibits cell proliferation, migration, and lumen formation induced by low concentrations of 4-HNE.
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Hypothyroxinemia is a common subclinical thyroid dysfunction in pregnant women. Epidemiological studies have shown that the offspring of maternal hypothyroxinemia have a significantly increased risk of autism, but mechanisms remain unclear. Studies from clinical and animals suggest that thyroid hormone deficiency may lead to irreversible damage to brain development, which may contribute to autism. This review explores the clinical evidence of gestational hypothyroxinemia and autism in offspring and the underlying mechanisms that promote the development and progression of autism. It also emphasizes the importance of early diagnosis and treatment of thyroid disease in pregnancy for the prevention of neurodevelopmental abnormalities in offspring.
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Objective:To investigate the effects of interferon gene stimulating protein (STING) inhibitor (C176) on human retinal microvascular endothelial cells (hRMEC) under oxidative stress.Methods:An animal experimental study. In vivo experiment: 48 healthy male C57BL/6J mice were randomly divided into wild type mice group (WT group) and diabetes (DM) group, with 24 mice in each group. DM mice were induced by streptozotocin to establish DM model. After successful modeling, DM group was divided into DM+dimethyl sulfoxide (DMSO) group and DM+C176 group, with 12 mice in each group. The mice in the DM+DMSO group were intraperitoneally injected with DMSO at the dose of 50 mg/kg. Mice in DM+C176 group were intraperitoneally injected with STING inhibitor C176 750 nmol at the dose of 50 mg/kg. Four weeks after modeling, immunohistochemical staining, Western blot and real-time fluorescence quantitative polymerase chain reaction were used to detect the expression of STING in the retina of WT and DM mice. The leukocyte adhesion test was used to detect the number of leukocytes adhering to hRMEC in mice with WT, DM+DMSO and DM+C176 groups. In vitro experiment: hRMEC was randomly divided into conventional culture cell group (N group), dimethyl sulfoxide (DMSO) group (with DMSO intervention) and C176 group (with C176 intervention). The cells were induced by 150 μg/ml glycation end products for each group. In vitro leukocyte adhesion test combined with 4', 6-diamino-2-phenylindole staining was used to detect the number of leukocytes adhering to hRMEC. The adherent leukocytes were quantitatively analyzed by flow cytometry; H 2DCFDA/reactive oxygen species (ROS) fluorescence probe was used to detect ROS expression in cells; Seahorse XFe96 cell energy metabolism analyzer was used to measure the level of intracellular glycolysis. t-test was used to compare the two groups; single factor analysis of variance was used to compare the three groups. Results:In vivo experiment: compared with WT group, the expression level of STING ( t=73.248) and the relative expression amount of mRNA ( t=67.385) in the retina of DM group mice increased significantly ( P<0.05). Compared with WT group, the number of leukocytes adhering to the retinal vessels of mice in DM+DMSO group was significantly increased, while that in DM+C176 group was significantly decreased ( F=84.352, P<0.01). In vitro: compared with N group and DMSO group, the number of leukocyte adhesion on hRMEC in C176 group decreased significantly ( F=35.251, P<0.01). Compared with N group, the number of leukocytes adhering to hRMEC in DMSO group and C176 group decreased significantly ( F=26.374, P<0.01). The ROS level in hRMEC in C176 group was significantly lower than that in N group and C176 group ( F=41.362, P<0.01). Compared with N group and DMSO group, the glycolysis level of hRMEC in C176 group was significantly reduced, with a statistically significant difference ( F=68.741, P<0.01). Conclusion:Inhibiting the expression of STING in retinal vascular endothelial cells can improve the progress of DM by inhibiting leukocyte adhesion, ROS production and glycolysis level.
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Objective:To investigate the clinical characteristics of elderly patients with coronavirus disease 2019(COVID-19), in order to provide scientific evidence for the diagnosis and treatment of COVID-19 in elderly patients.Methods:Clinical data of 102 patients with COVID-19 admitted to the B11 East Ward of the Zhongfaxincheng campus and the E1-3 ward of the Guanggu Campus of Tongji Hospital affiliated to Huazhong University of Science and Technology in Wuhan from 1 February 2020 to 28 February 2020 were retrospectively collected and analyzed.Patients were categorized into 2 groups: the elderly group(≥60 years old)and the young and middle-aged group(<60 years old). Differences in epidemiological features, demographics, clinical symptoms, laboratory results and imaging findings between the two groups were retrospectively analyzed.Results:Among 102 patients with COVID-19, 58 were in the elderly group(≥60 years old), with a median age of 67.0(63.8, 71.0)years old, and 44 in the young and middle-aged group(<60 years old), with a median age of 47.5(38.0, 51.8)years old.There was no significant difference in gender ratio between the two groups( χ2=0.033, P=0.855). Of 102 patients, 42.0%(21/50)had close contact with an infected person, 14.0%(7/50)were from infection clusters, and 18.0%(9/50)had suspected hospital-acquired infections.Fever and cough remained the most common symptoms, but gastrointestinal symptoms such as nausea, poor appetite, diarrhea and muscle cramps were also warning signs.Fatigue and cough were the most common presenting symptoms in elderly male patients.Bilateral patchy infiltrates(57.9%, 22/38)and ground-glass opacities(42.1%, 16/38)were the main imaging features and 42.1%(16/38)patients had multiple areas of the lungs involved.Over 50% patients had increased levels of blood glucose, D-dimer, fibrinogen, C-reactive protein, procalcitonin, multiple cytokines and neutrophil-to-lymphocyte ratio, as well as decreased levels of albumin, hemoglobin, hematocrit, lymphocytes and serum calcium.Compared with the young and middle-aged group, the elderly group had higher rates of abnormality in levels of D-dimer and serum calcium( χ2=7.067 and 4.166, P=0.008 and 0.041). Conclusions:Fever and cough are the most common symptoms in elderly patients with COVID-19.Elderly patients with COVID-19 have multiple abnormalities in clinical laboratory test results, which show a certain level of specificity compared with young and middle-aged patients.
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Objective:To investigate the relationship of interleukin (IL)-37, osteoprotegerin with coronary artery disease and its stenosisdegree.Methods:The prospective research method was used. From April 2018 to June 2019, two hundred and eleven suspected or diagnosed coronary artery disease patients who had chest pain or discomfort in Dalian Friendship Hospital were selected. The patients underwent selective percutaneous coronary angiography and completed coronary stenosis score (Gensini score). According to the degree of coronary stenosis, 211 patients were divided into the control group(coronary stenosis<50%, 45 cases), single-vessel stenosis group (single-vessel stenosis ≥ 50%, 52 cases), double-vesselstenosis group (double-vesselstenosis ≥ 50%, 58 cases), and triple-vessel stenosis group (triple-vessel stenosis ≥ 50%, 56 cases). The levels of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein a, uric acid, creatinine were measured by the automatic biochemical analyzer. The serum levels of IL-37 and osteoprotegerin were detected by enzyme-linked immunosorbent assay.Results:There were no statistical differences in FBG, uric acid, creatinine, TC, TG, LDL-C, HDL-C, ApoA1 and ApoB among 4 groups ( P>0.05). In the control group, single-vessel stenosis group, double-vessel stenosis group and triple-vessel stenosis group, lipoprotein a was (0.266 ± 0.060), (0.283 ± 0.070), (0.289 ± 0.066) and (0.307 ± 0.084) mg/L respectively; coronary stenosis score was (8.27 ± 7.08), (437.45 ± 98.47), (493.72 ± 125.19) and (522.61 ± 149.34) scores respectively; IL-37 was (342.27 ± 122.36), (437.45 ± 98.47), (493.72 ± 125.19) and (522.61 ± 149.34) ng/L respectively; osteoprotegerin was (378.29 ± 111.95), (458.39 ± 115.37), (502.50 ± 116.88) and (533.39 ± 139.83) ng/L respectively; and there were statistical differences among 4 groups ( P<0.05 or <0.01). IL-37, osteoprotegerin and lipoproteina were positively correlated with coronary stenosis score ( r = 0.43, 0.42 and 0.23, P<0.05), the osteoprotegerin was positively correlated with IL-37( r = 0.73, P<0.05). The multivariate linear regression analysis result showed that the IL-37 and osteoprotegerin were independent protective factors of coronary stenosis degree( β = 0.07 and 0.07, t = 2.72 and 2.57, P<0.01 or <0.05),and lipoproteina was independent risk factor of coronary stenosis degree ( β = 0.97, t = 2.89, P<0.01). Conclusions:IL-37 and osteoprotegerin are positively correlated with the degree of coronary stenosis. They are anti-inflammatory and protective factors of coronary heart disease.
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Objective@#To investigate the characteristics of intestinal microflora in patients with neuromyelitis optica spectrum disorders (NMOSDs) and related clinical significance.@*Methods@#The data about basic clinical features, fecal specimens as well as cerebrospinal fluid samples of 28 patients with NMOSDs, 15 patients with multiple sclerosis (MS) and 16 healthy controls admitted to the Department of Neurology, the First Affiliated Hospital of Zhengzhou University from July 2017 to January 2019 were collected. The differences about intestinal microbial characteristics and inflammatory index levels in each group were analyzed. The relevance between the diversity of intestinal microbiota and inflammatory index was explored.@*Results@#Compared with healthy controls, the intestinal microfloras of patients with NMOSDs and MS respectively were structurally disordered. The levels of the microbial diversity (chao 1 index) were significantly decreased in patients with NMOSDs compared with healthy controls, while their inflammation indexes, including IL-6, IL-10 and transforming growth factor (TGF)-α, in cerebrospinal fluid were significantly increased ((12.9±4.6) pg/ml vs (2.6±1.8) pg/ml, t=4.197, P=0.001; (3.4±2.1) pg/ml vs (0.9±0.2) pg/ml, t=2.265, P=0.037; (21.4±12.7) ng/ml vs (13.7±7.8) ng/ml, t=3.702, P=0.004). Compared with control group, the relative abundance of butyrivibrio, prevotella and anaerostipes was decreased significantly in NMOSDs group (6.8%±3.5% vs 13.0%±4.7%, t=4.941, P<0.001; 3.9%±2.2% vs 6.9%±3.3%, t=3.282, P=0.003; 5.1%±2.5% vs 7.3%±3.0%, t=2.641, P=0.012), while the relative abundance of ackermania was increased obviously (7.0%±3.1% vs 4.4%±2.8%, t=2.802, P=0.008); Besides, the quantitative Streptococcus thermophilus and butyrivibrio reduced in MS group (3.4%±2.4% vs 5.5%±2.1%, t=2.784, P=0.009; 7.9%±5.4% vs 13.0%±4.7%, t=2.501, P=0.018). In the comparison between subgroups, the relative abundance of bacteroides of aquaporin (AQP) 4-IgG-positive patients was lower than that of AQP4-IgG-negative patients (23.1%±8.9% vs 32.6%±10.4%, t=2.572, P=0.016), while the former subgroup had the higher level of the relative abundance of bifidobacterium (3.4%±1.6% vs 1.7%±1.4%, t=2.977, P=0.006). Moreover, there was a significant relevance between the diversity of intestinal microflora and the level of inflammatory factor IL-6 in cerebrospinal fluid (r=-0.548, P=0.003).@*Conclusions@#The intestinal microflora structural disorder and diversity reduction exist in patients with NMOSDs. Moreover, there is a significant correlation between the intestinal microflora and the level of inflammatory factors in NMOSDs, which can be used as an important means of clinical auxiliary examination.
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OBJECTIVE@#To determine the types and frequency of deafness-related variants among 7875 newborns from Dongying area of Shandong Province.@*METHODS@#One hundred loci of 18 common deafness genes were subjected to semiconductor sequencing. Variant site, frequency and distribution of the variants were analyzed.@*RESULTS@#In total 552 deafness gene variants were detected among the 7875 newborns, which yielded a detection rate of 7.01%. Among these, common variant sites for GJB2, SLC26A4 and GJB3 genes were c.235delC, IVS7-2A>G and c.538C>T, respectively. The variant frequencies of matrilinear inheritance deafness genes MT-CO1, MT-RNR1, MT-TL1 and MT-TS1 were 0.38%, 0.25%, 0.1% and 0.01%, respectively. Four newborns were diagnosed with deafness, among which one had unilateral hearing loss. Analysis of the proportions of neonatal deafness-related variants in five counties of Dongying showed that the highest variant rate for the SLC26A4 gene compared with GJB2 was in Lijin county (51.76% vs. 40%), while the lowest was in Hekou county (30.77% vs. 56.41%).@*CONCLUSION@#The carrier rate of deafness-related variants in Dongying area is higher than other regions of China, which may be attributed to the increased types and variant sites covered by the semiconductor sequencing method compared with the chip method and time-of-flight mass spectrometry. Due to geographical and population aggregation factors, the proportion of deafness variants in the five counties of Dongying differed significantly. Above results may provide a guide for the prevention of congenital deafness in Dongying area.
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Ocular opsoclonus is a rare disorder of the saccadic system, in which fixation is continuously interrupted by involuntary, chaotic, rapid and multi-directional saccadic eye movements, interrupting the gaze-holding function, leading to“dancing eyes”. Ocular opsoclonus has rarely been reported in China. A case of ocular opsoclonus associated with anti-N-methyl-D-aspartate receptor encephalitis is reported to improve awareness about the ocular sign. The patient′s condition reached the peak at the 5th week. He developed ocular opsoclonus on the basis of nonconvulsive status epilepticus, accompanied by frequent involuntary movements of the mouth and limbs. The ocular opsoclonus gradually relieved on the 7th week with the active treatment.
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Objective To investigate the characteristics of intestinal microflora in patients with neuromyelitis optica spectrum disorders (NMOSDs) and related clinical significance.Methods The data about basic clinical features,fecal specimens as well as cerebrospinal fluid samples of 28 patients with NMOSDs,15 patients with multiple sclerosis (MS) and 16 healthy controls admitted to the Department of Neurology,the First Affiliated Hospital of Zhengzhou University from July 2017 to January 2019 were collected.The differences about intestinal microbial characteristics and inflammatory index levels in each group were analyzed.The relevance between the diversity of intestinal microbiota and inflammatory index was explored.Results Compared with healthy controls,the intestinal microfloras of patients with NMOSDs and MS respectively were structurally disordered.The levels of the microbial diversity (chao 1 index) were significantly decreased in patients with NMOSDs compared with healthy controls,while their inflammation indexes,including IL-6,IL-10 and transforming growth factor (TGF)-α,in cerebrospinal fluid were significantly increased ((12.9±4.6) pg/ml vs (2.6±1.8) pg/ml,t=4.197,P=0.001;(3.4±2.1) pg/ml vs (0.9±0.2)pg/ml,t=2.265,P=0.037;(21.4± 12.7) ng/ml vs (13.7±7.8) ng/ml,t=3.702,P=0.004).Compared with control group,the relative abundance of butyrivibrio,prevotella and anaerostipes was decreased significantly in NMOSDs group (6.8％±3.5％ vs 13.0％±4.7％,t=4.941,P＜0.001;3.9％±2.2％ vs 6.9％±3.3％,t=3.282,P=0.003;5.1％±2.5％ vs 7.3％±3.0％,t=2.641,P=0.012),while the relative abundance of ackermania was increased obviously (7.0％±3.1％ vs 4.4％±2.8％,t=2.802,P=0.008);Besides,the quantitative Streptococcus thermophilus and butyrivibrio reduced in MS group (3.4％±2.4％ vs 5.5％±2.1％,t=2.784,P=0.009;7.9％±5.4％ vs 13.0％±4.7％,t=2.501,P=0.018).In the comparison between subgroups,the relative abundance of bacteroides of aquaporin (AQP) 4-IgG-positive patients was lower than that of AQP4-IgG-negative patients (23.1％±8.9％ vs 32.6％± 10.4％,t=2.572,P=0.016),while the former subgroup had the higher level of the relative abundance of bifidobacterium (3.4％± 1.6％ vs 1.7％± 1.4％,t=2.977,P=0.006).Moreover,there was a significant relevance between the diversity of intestinal microflora and the level of inflammatory factor IL-6 in cerebrospinal fluid (r=-0.548,P=0.003).Conclusions The intestinal microflora structural disorder and diversity reduction exist in patients with NMOSDs.Moreover,there is a significant correlation between the intestinal microflora and the level of inflammatory factors in NMOSDs,which can be used as an important means of clinical auxiliary examination.
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Objective:To study the clinical characteristics and compliance of early-onset gout patients by case-control analysis.Methods:A total of 111 early-onset patients (onset age ≤35 years old) were included as Group A, and 111 non-early-onset patients (onset age >35 years old) with matched disease durationwere included as Group B. The differences ofclinical characteristics, causes of acute gout attack, dairy diet habits, compliance, and misunderstanding of the disease were compared.Results:Compared with the non-early-onsetgoutpatients, the early-onset patients had a higher proportion of obesity (63 cases vs 28 cases), family history (36 cases vs 20 cases) and tophus (39 cases vs 23 cases) and higher level of VAS scores (8.5±1.3 vs 7.6±1.7; χ2=22.988, P<0.01; χ2=5.749, P=0.016; χ2=5.729, P=0.017; t=4.639, P<0.01), lowerproportionof the first metatarsophalangeal joint involvement as the initial joint involvement (45.9%, 51 cases vs 59.4%, 66 cases; χ2=4.066, P=0.044), higher proportion of the ankle involvement as the initial joint involvement (34.2%, 38 cases vs 21.6%, 24 cases; χ2=4.386, P=0.036), higher proportion of alcohol drinkers and high fructose drinkers, which was more likely to relate to alcohol intake, strenuous exercise and high fructose intakeas trigger of the flare ( χ2=6.513, P=0.011; χ2=7.126, P=0.008; χ2=1.978, P=0.160), while the proportion of regular exercisers and on diet in the family was lower ( χ2=22.887, P<0.01; t=-4.917, P<0.01). The proportion of poor diet and medication compliance in Group A was higher than that in Group B(57.7%, 64 cases vs 38.7%, 43 cases; χ2=5.207, P=0.022; χ2=5.867, P=0.015). As for the reason for poor treatment compliance, early-onset gout patients were more worry about the side-effects of drugs than non-early onset patients ( χ2=4.190, P=0.041). There was no significant difference between the two groups in the main misunderstanding of gout. Conclusion:Although early onset gout patients are young, their condition is more serious, and compliance is poorer, this group of patients should be highly valued in clinical diagnosis and treatment.
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Objective To investigate the effects of betulinic acid on spatial learning and memory in rats with type 2 diabetes mellitus(T2DM) and to explore its underlying mechanisms.Methods Forty-five male Wistar rats were randomly divided into control group (Sham),T2DM group and betulinic acid treatment group (BA) with 15 in each group.The rats in the latter two groups were given a high fat diet plus low dose of streptozotocin (STZ) to induce T2DM,and the rats in BA group was given 10 mg/kg BA for intragastric administration once daily for 12 weeks,the rats in T2DM group and Sham group were given an equal volume of physiological saline.Morris water maze method was used to detect the cognitive function.The mRNA levels of synaptic plasticity related protein GAP-43,SYP and PSD-95 were detected by RT-PCR.The protein expressions of cholinergic neurotransmitter ChAT and Ach were detected by Elisa.Results Compared with the Sham group,the escape latency of the T2DM group was significantly prolonged on days 2-4 ((62.28 ± 2.97)s vs (47.09±2.16)s;(48.52±3.09) s vs (26.18±2.21)s;(42.31±2.80)s vs (13.42±1.23)s),the original platform quadrant time was significantly reduced ((24.60±2.42) s vs (41.85 ± 1.98) s),GAP-43,SYP,ChAT and Ach levels were significantly lower,the differences were statistically significant (the t values were 16.37,22.34,39.78,20.42,116.01,91.35,71.84,21.88 and 21.11,respectively,all P＜ 0.05).Compared with T2DM group,the escape latency of BA group in 2-4 days were significantly shortened ((55.61±2.75)s vs (62.28±2.97)s;(31.35±2.63)s vs (48.52±3.09)s;(42.31±2.80)s vs (16.58± 1.37) s),the original platform quadrant time increased significantly ((37.58± 2.31) s vs (24.60±2.42) s),and GAP-43,SYP,PSD-95,ChAT and Ach levels were significantly higher,and the differences were statistically significant (the t values were 6.80,16.21,33.54,14.55,41.83,35.23,36.20,12.82 and 9.97,respectively,all P＜0.05).Conclusion Betulinic acid can improve the spatial learning and memory of type 2 diabetic rats,and increasing the expression of GAP-43,SYP,PSD-95,ChAT and Ach may be its potential mechanism.
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Objective@#To analyze the changes of protein expression in aqueous humor of patients with primary open angle glaucoma (POAG), and to explore the biological markers and potential therapeutic targets associated with disease occurrence.@*Methods@#A retrospective case-control study was adopted.Ten patients with age-related cataract and 10 patients with POAG combined with cataract.were collected at the Tianjin Medical University Eye Hospital from October 2016 to December 2017.In the process of surgery, 100 μl of aqueous humor were collected with 1 ml syringe and No.1 needle through the surgical access.Those proteins extracted from aqueous humor were analyzed by quantitative proteomic mass spectrometry.The differential significance test was performed by Maxquant significances A. The differential proteins of the two groups were screened and determined with the conditions of P<0.05 and difference multiple>2.The biological big data was annotated by the function of GO and KEGG.The study was approved by the Ethics Committee of the Tianjin Medical University Eye Hospital (No.2013KY[L]-10). Patients and their guardians all signed the informed consent.@*Results@#Ninty-seven differential proteins were detected in this proteomic analysis, including 48 up-regulated proteins and 49 down-regulated proteins.GO analysis significantly differs in protein function involved in many aspects, some different proteins including lipopolysaccharide-binding protein (LBP), cluster of Differentiation 163(CD163), C-reactive protein (CRP), annexin A1 (ANXA1) were involved in inflammation; redox-related proteins were glutathione S-transferase P (GSTP1), thioredoxin (TXN), some different proteins related with cell adhesion movement were cartilage oligomeric matrix protein (COMP), desmocollin-2 (DSC2) and laminin subunit beta-2 (LAMB2); procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1), solid protein (tenascin, TNC) are associated with fibrosis; some different proteins related to nerve growth were reelin (RELN), semaphorin-3F(SEMA3F), semaphorin-4B(SEMA4B). Metabolism-related proteins included pyruvate kinase (PKM), carb oxypeptidase N subunit 2 (CPN2) and so on.KEGG analysis indicated that the expression of NrF2/ERK signaling pathway and TGF-β/NF-κB signaling pathway were different between the two groups.@*Conclusions@#The expression of GSTP1 and TXN in the aqueous humor of POAG is significantly decreased, which may regulate cell adhesion and activity and expression of extracellular matrix by regulating NrF2/ERK1/2 and TGF-β/NF-κB signaling pathways.GSTP1 and TXN may serve as a potential biomarker and therapeutic target of POAG.
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Objective To analyze the changes of protein expression in aqueous humor of patients with primary open angle glaucoma ( POAG ) , and to explore the biological markers and potential therapeutic targets associated with disease occurrence. Methods A retrospective case-control study was adopted. Ten patients with age-related cataract and 10 patients with POAG combined with cataract. were collected at the Tianjin Medical University Eye Hospital from October 2016 to December 2017. In the process of surgery,100 μl of aqueous humor were collected with 1 ml syringe and No. 1 needle through the surgical access. Those proteins extracted from aqueous humor were analyzed by quantitative proteomic mass spectrometry. The differential significance test was performed by Maxquant significances A. The differential proteins of the two groups were screened and determined with the conditions of P<0. 05 and difference multiple>2. The biological big data was annotated by the function of GO and KEGG. The study was approved by the Ethics Committee of the Tianjin Medical University Eye Hospital (No. 2013KY[L]-10). Patients and their guardians all signed the informed consent. Results Ninty-seven differential proteins were detected in this proteomic analysis,including 48 up-regulated proteins and 49 down-regulated proteins. GO analysis significantly differs in protein function involved in many aspects,some different proteins including lipopolysaccharide-binding protein (LBP),cluster of Differentiation 163(CD163),C-reactive protein (CRP),annexin A1 (ANXA1) were involved in inflammation;redox-related proteins were glutathione S-transferase P (GSTP1),thioredoxin (TXN), some different proteins related with cell adhesion movement were cartilage oligomeric matrix protein ( COMP ) , desmocollin-2 ( DSC2 ) and laminin subunit beta-2 ( LAMB2 );procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1),solid protein (tenascin,TNC) are associated with fibrosis;some different proteins related to nerve growth were reelin (RELN),semaphorin-3F(SEMA3F),semaphorin-4B(SEMA4B). Metabolism-related proteins included pyruvate kinase ( PKM ) , carb oxypeptidase N subunit 2 ( CPN2 ) and so on. KEGG analysis indicated that the expression of NrF2/ERK signaling pathway and TGF-β/NF-κB signaling pathway were different between the two groups. Conclusions The expression of GSTP1 and TXN in the aqueous humor of POAG is significantly decreased,which may regulate cell adhesion and activity and expression of extracellular matrix by regulating NrF2/ERK1/2 and TGF-β/NF-κB signaling pathways. GSTP1 and TXN may serve as a potential biomarker and therapeutic target of POAG.
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Objective To observe the effects of urate-lowering therapy ( ULT) on indexes of inflammation, the frequency of gout flares, compliance of ULT, and the achieved rates of serum uric acid in patients at acute stage. Methods 151 patients with acute gout flares were randomly divided into observation group ( 60 cases with ULT in the acute phase) and control group (91 cases with ULT after 2 weeks of complete remission from acute flares). Visual analogue pain scores (VAS), joint swelling scores, white blood cell counts, erythrocyte sedimentation rates (ESR), as well as high sensitive-C reactive protein (hs-CRP) were measured respectively and compared between two groups. The observation group was treated with 40 mg/d of febuxostat for 12 weeks after effectively achieved inflammation ( VAS<3 points) , while the control group was treated with the same therapy after 2 weeks of symptoms complete remission from acute gout flares. Finally, these indexes were followed and recorded, including the number of gout flares, the compliance of ULT, the changes of liver and kidney function, and the proportion of patients with serum uric acid<360μmol/L. Results There was no statistical difference in the baseline condition, VAS pain scores, joint swelling scores, white blood cell counts, ESR, and hs-CRP between two groups after different ULTs ( all P>0.05) . There was no statistical difference in the frequency of gout flares between two groups during the ULT of 12 weeks ( P=0.658) . At the end of 12 weeks, the serum uric acid in the observation group was significantly lower compared with the control group [(318.38±95.16 vs 398.12±120.13)μmol/L,P<0.01]. The compliance rate of ULT and the rate of reaching the standard of serum uric acid<360μmol/L in the observation group were higher than those in the control group ( both P<0.01) . Conclusion The treatment of ULT with patients after effective achieved of acute gout inflammation has no detrimental effects on VAS pain, joint swelling score, the conversion of inflammation index, and the number of gout flares, while improving the compliance of ULT and the achieved rate of serum uric acid.
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Objective To explore the role of forkhead box F2 (FoxF2) in the extracellular matrix of trabecular meshwork.Methods The cultured human trabecular meshwork cells (HTMCs) were divided into Scramble control group and FoxF2 small hairpin RNA (shRNA) group,then FoxF2 shRNA,the FoxF2 restructuring interference carrier was built,HTMCs were infected with FoxF2 shRNA lentivirus.Western blot assay was used to detect the expression of FoxF2 protein and extracellular matrix.Furthermore,Transwell counting experiment was used to analyze the migration ability of HTMCs.Results The cultured HTMCs grew well and showed a long spindle shape.The growth status of HTMCs was well,and their morphological characteristics were consistent with the HTMCs in vivo.The relative expression level of FoxF2 protein in the FoxF2 shRNA group was lower than that in the Scramble control group,with a significant difference between them (0.72 ± 0.02 vs.1.27 ± 0.05;t =16.68,P ＜ 0.01).The relative expression level of fibronectin (FN),collagen type Ⅰ (COL Ⅰ) and α-smooth muscle actin (α-SMA) were 0.43±0.03,0.53 ±0.08 and O.86±0.15 in the FoxF2 shRNA group,and 0.87±0.04,1.66±0.06 and 1.73 ±0.13 in the Scramble control group,respectively,the relative expression levels of FN,COL Ⅰ and α-SMA in the FoxF2 shRNA group were significantly lower than those in the Scramble control group (t =15.08,18.81,7.50,all at P＜0.01).The migration number of HTMCs in the FoxF2 shRNA group was significantly lower than that in the Scramble control group (117.30±11.41 vs.251.00±10.37;t =8.72,P＜0.01).Conclusions The FoxF2 shRNA lentivirus are successfully constructed,which can decrease the expression of FoxF2 in HTMCs.Low expression of FoxF2 can reduce the expression level of extracellular matrix protein in HTMCs and inhibit the migration ability of HTMCs.
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Objective To identify the efficacy and safety of implant vagus nerve stimulation (IVNS) for intractable epilepsy.Methods Eligible patients with intractable epilepsy during 2012-2015 were enrolled,and the information of preoperative evaluation was collected as baseline.During IVNS therapy,the process of seizures,the epileptic discharges of electroencephalogram (EEG),the complications and the changes of antiepileptic drugs or device parameters were recorded.The responder rate,the mean seizure reduction and the change of epileptic discharges were chosen as the indictors.Results Efficacy analyses were done in 33 patients,and the average age of these patients was 17.79 years.Seizure control improved over time with mean seizure reduction of 11.9％,17.3％,35.5％,38.1％,45.4％ and 50.0％,and responder rates of 18.2％(6/33),27.3％(9/33),41.4％(12/29),38.5％(10/26),7/18,and 10/17 at 1,3,6,12,24,36 months of IVNS therapy,respectively.In addition,the mean epileptic discharge reduction in EEG was 0.4％ and 13.0％,while the rate of patients who had epileptic discharge reduction of ≥50％ was 15.3％ and 23.1％ at 6,12 months of IVNS therapy,respectively.Conclusions IVNS is effective and safe.Furthermore,the efficacy of IVNS is time-dependent.
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Epilepsy is a common chronic brain disorder with multiple causes,and now autoimmune factors are believed to be an independent cause for epilepsy.Accumulating data support an autoimmune basis in patients with antiepileptic drug-resistant seizures.Moreover,systemic autoimmune diseases and epilepsy co-occur frequently.Neural specific autoantibodies can also mediate the process of seizures through different pathways,The diagnosis of autoimmune epilepsy is based on frequency of antiepileptic drug-resistant seizures,the presence of neural specific autoantibodies,inflammatory changes in serum or spinal fluid or on magneticresonanceimaging,the change in electroencephalogram,a personal or family history of autoimmunity.Once autoimmune epilepsy is diagnosed,the immunotherapy is required.Early immunotherapy is crucial for improving the prognosis of the patients.