摘要
Objective:To evaluate the developmental toxicity of Cry1Ab protein by studying its effects on cell proliferation and differentiation ability using a developmental toxicity assessment model based on embryonic stem-cell.Methods:Cry1Ab protein was tested in seven dose groups(31.25,62.50,125.00,250.00,320.00,1 000.00,and 2 000.00 μg/L)on mouse embryonic stem cells D3(ES-D3)and 3T3 mouse fibroblast cells,with 5-fluorouracil(5-FU)used as the positive control and phos-phate buffer saline(PBS)as the solvent control.Cell viability was detected by CCK-8 assay to calculate the 50%inhibitory concentration(IC50)of the test substance for different cells.Additionally,Cry1 Ab protein was tested in five dose groups(125.00,250.00,320.00,1 000.00,and 2 000.00 μg/L)on ES-D3 cells,with PBS as the solvent control and 5-FU used for model validation.After cell treatment,cardiac differentiation was induced using the embryonic bodies(EBs)culture method.The growth of EBs was observed under a microscope,and their diameters on the third and fifth days were measured.The proportion of EBs differentiating into beating cardiomyocytes was recorded,and the 50%inhibition con-centration of differentiation(ID50)was calculated.Based on a developmental toxicity discrimination func-tion,the developmental toxicity of the test substances was classified.Furthermore,at the end of the cul-ture period,mRNA expression levels of cardiac differentiation-related markers(Oct3/4,GATAA-4,Nkx2.5,and β-MHC)were quantitatively detected using real-time quantitative polymerase chain reaction(qPCR)in the collected EBs samples.Results:The IC50 of 5-FU was determined as 46.37 μg/L in 3T3 cells and 32.67 μg/L in ES-D3 cells,while the ID50 in ES-D3 cells was 21.28 μg/L.According to the discrimination function results,5-FU was classified as a strong embryotoxic substance.There were no sta-tistically significant differences in cell viability between different concentrations of Cry 1 Ab protein treat-ment groups and the control group in both 3T3 cells and ES-D3 cells(P>0.05).Moreover,there were no statistically significant differences in the diameter of EBs on the third and fifth days,as well as their morphology,between the Cry1Ab protein treatment groups and the control group(P>0.05).The cardi-ac differentiation rate showed no statistically significant differences between different concentrations of Cry1Ab protein treatment groups and the control group(P>0.05).5-FU significantly reduced the mRNA expression levels of β-MHC,Nkx2.5,and GATA-4(P<0.05),showing a dose-dependent trend(P<0.05),while the mRNA expression levels of the pluripotency-associated marker Oct3/4 exhibited an increasing trend(P<0.05).However,there were no statistically significant differences in the mRNA expression levels of mature cardiac marker β-MHC,early cardiac differentiation marker Nkx2.5 and GATA-4,and pluripotency-associated marker Oct3/4 between the Cry1Ab protein treatment groups and the control group(P>0.05).Conclusion:No developmental toxicity of Cry1Ab protein at concen-trations ranging from 31.25 to 2 000.00 μg/L was observed in this experimental model.
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Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.
Subject(s)
Mice , Animals , Diabetes Mellitus, Experimental/metabolism , Axons/physiology , Diabetic Neuropathies , Sensory Receptor Cells/metabolism , Neuralgia/metabolism摘要
OBJECTIVE@#To explore the clinical and genetic characteristics of three children with KBG syndrome.@*METHODS@#Clinical data of the three children from two families who have presented at the First Affiliated Hospital of Zhengzhou University between October 2019 and September 2020 and their family members were collected. Trio-whole exome sequencing (trio-WES) and Sanger sequencing were carried out.@*RESULTS@#All children had feeding difficulties, congenital heart defects and facial dysmorphism. The sib- pair from family 1 was found to harbor a novel de novo heterozygous c.6270delT (p.Q2091Rfs*84) variant of the ANKRD11 gene, whilst the child from family 2 was found to harbor a novel heterozygous c.6858delC (p.D2286Efs*51) variant of the ANKRD11 gene, which was inherited from his mother who had a mild clinical phenotype.@*CONCLUSION@#The heterozygous frameshift variants of the ANKRD11 gene probably underlay the disease in the three children. Above findings have enriched the spectrum of the ANKRD11 gene variants.
Subject(s)
Female , Child , Humans , Abnormalities, Multiple/genetics , Intellectual Disability/genetics , Bone Diseases, Developmental/genetics , Tooth Abnormalities/genetics , Facies , Repressor Proteins/genetics , Mothers , Mutation摘要
Objective:To investigate the degenerative characteristics and biomechanical effects of paravertebral muscles in patients with degenerative lumbar scoliosis.Methods:The clinical data of 236 patients with degenerative lumbar scoliosis from January 2016 to January 2020 in Yuncheng Central Hospital of Shanxi Province were retrospectively analyzed. All patients underwent lumbar X-ray and MRI measurement, and the indexes included coronal scoliosis Cobb angle, rotation classification of apical vertebra, cross-sectional area (CSA) of the apical vertebra upper and lower intercalated disc plane, fatty infiltration rate (FIR) of psoas major and back extensor muscle group (including erector spinae and multifidus muscle), cross-sectional area difference index (CDI) and fatty infiltration difference (FID). The correlation between paravertebral muscle degeneration and coronal scoliosis Cobb angle was evaluated.Results:The coronal scoliosis Cobb angle of 236 patients was 10.4° to 57.8° (18.72 ± 6.44)°; there were no statistical differences in coronal scoliosis Cobb angle and rotation classification of apical vertebra between different sex, scoliosis direction and apical vertebra position ( P>0.05). In the apical vertebra upper intercalated disc plane, the concave side CSA of psoas major muscle was significantly higher than convex side: (3.82 ± 1.06) cm 2 vs. (3.68 ± 1.01) cm 2, the concave side CSA of multifidus muscle, back extensor muscle group and paraspinal muscle group (including psoas major muscle, quadratus lumborum, erector spinae and multifidus muscle) was significantly lower than convex side: (9.80 ± 2.14) cm 2 vs. (10.46 ± 2.60) cm 2, (18.18 ± 3.03) cm 2 vs. (19.79 ± 3.22) cm 2 and (25.25 ± 5.06) cm 2 vs. (27.86 ± 6.90) cm 2, and there were statistical differences ( P<0.05 or <0.01); there were no statistical differences in CSA of quadratus lumborum and erector spinae between concave side and convex side ( P>0.05). In the apical vertebra lower intercalated disc plane, the concave side CSA of psoas major muscle and quadratus lumborum was significantly higher than convex side: (6.62 ± 3.09) cm 2 vs. (6.40 ± 3.23) cm 2 and (4.58 ± 0.57) cm 2 vs. (4.45 ± 0.64) cm 2, the concave side CSA of multifidus muscle and back extensor muscle group was significantly lower than concave side: (9.49 ± 3.10) cm 2 vs. (10.32 ± 4.06) cm 2 and (19.31 ± 4.36) cm 2 vs. (20.54 ± 5.60) cm 2, and there were statistical differences ( P<0.01 or <0.05); there was no statistical difference in CSA of erector spinae and paraspinal muscle group between concave side and convex side ( P>0.05). In apical vertebra upper and lower intercalated disc plane, the concave side FIR of back extensor muscle group was significantly higher than convex side: (31.83 ± 11.04)% vs. (24.37 ± 12.76)% and (38.62 ± 10.09)% vs. (31.80 ± 8.23)%, and there was statistical difference ( P<0.01); there was no statistical difference in FIR of psoas major muscle between concave side and convex side ( P>0.05). Pearson linear correlation analysis result showed that CDI of multifidus muscle, back extensor muscle group, paraspinal muscle group and FID of back extensor muscle group were positively correlated with coronal scoliosis Cobb angle (apical vertebra upper intercalated disc plane: r = 0.94, 0.70, 0.86 and 0.90, P<0.01; apical vertebra lower intercalated disc plane: r = 0.92, 0.94, 0.81 and 0.66, P<0.01); the CDI of psoas major muscle in apical vertebra lower intercalated disc plane was positively correlated with coronal scoliosis Cobb angle ( r = 0.73, P<0.01); there was no correlation between CDI of psoas major muscle in apical vertebra upper intercalated disc plane and coronal scoliosis Cobb angle ( r = 0.17, P>0.05). In patients with apical vertebra located in L 2 and L 3, the CSA of psoas major muscle and quadratus lumborum in apical vertebra lower intercalated disc plane was significantly higher than that in apical vertebra upper intercalated disc plane, and there was statistical difference ( P<0.01); in patients with apical vertebra located in L 2, the concave side CSA of erector spinae in apical vertebra lower intercalated disc plane was significantly higher than that in apical vertebra upper intercalated disc plane, and there was statistical difference ( P<0.01). Conclusions:The biomechanical effects of lumbar flexion/ back extensor muscle group should be different in the process of disease progression in patients with degenerative lumbar scoliosis, in which the back extensor muscle group can effectively inhibit the degenerative disease. The protection of paravertebral muscle group function should be placed in an important role in degenerative lumbar scoliosis treatment.
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Objective: To observe the feasibility of oral administration of diluted gadolinium diamine injection as negative contrast agent for gastrointestinal tract for improving imaging quality and displaying pancreaticobiliary duct during magnetic resonance cholangiopancreatography (MRCP) in children. Methods: MRI of gadolinium diamine diluent with concentrations of 0.20%, 0.30% and 0.50% and pure water were performed at the same time, then the signal attenuation rate of each concentration of contrast agent was calculated. A total of 282 children received MRCP were divided into experimental group (244 children with suspected hepatobiliary diseases) and control group (38 children with non-hepatobiliary diseases). One hour before examination, children in experimental group were asked to orally take 0.50% gadolinium diamine diluent 400 ml within 45 min, and then underwent MRCP 15 min later. All images were scored by 2 imaging physicians, and the imaging qualified rate of was calculated taken ≥3 points and not affecting diagnosis as qualified standards. Kappa coefficient was used to test the consistency of image quality assessments of 2 doctors, and the differences of imaging qualified rate were compared between 2 groups and different genders. Results: The signal attenuation rate of the concentration of 0.20%, 0.30% and 0.50% gadolinium diamine diluents was 76.67%, 88.47% and 98.33%, respectively. The 0.50% gadolinium diamine diluent had the best water inhibition effect, and was selected as the negative contrast agent for children gastrointestinal tract. The consistency of Results: of imaging quality scores by 2 doctors was good (Kappa=0.85, P0.05). Conclusion: Oral administration of 0.5% concentration of gadolinium diamine diluent can effectively inhibit high gastrointestinal fluid signals and significantly improve imaging quality of MRCP in children.
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Objective@#To discuss the characteristics of symptoms improvement based on the follow-up evaluation of Eustachian tube balloon dilation medium to long-term efficacy in patients with symptomatic Eustachian tube dysfunction (SETD).@*Methods@#Patients from 2015 to 2017 were followed up after Eustachian tube balloon dilation (with the sense of aural fullness, or tinnitus and hearing ambiguity). All participants had been done ETDQ-7 before surgery and were re-evaluated with ETDQ-7 in follow-up. The improvement of overall and individual symptoms scores in ETDQ-7, the effects of gender and the difference of scores at different stages (12-18 months, 18-24 months and 24-30 months) after the operation were analyzed.@*Results@#There were 29 patients, including 16 males and 13 females, whose age ranged from 20 to 62 years old. The medium to long-term score of ETDQ-7 significantly declined after surgery (27.0±7.9 vs. 14.1±7.5, P<0.05). Among all symptoms, symptoms like "blockage feeling in ear or being like under the water, constriction feeling" , "sound of blisters or explosions in the ear" decreased obviously (P<0.05). Comparing different stages after surgery, the scores of ETDQ-7 existed no difference (P>0.05). And the difference of gender showed no significant influence on surgery effects.@*Conclusion@#The subjective symptoms of patients with Eustachian tube dysfunction diagnosed with SETD can be significantly improved in the medium to long-term follow-up after Eustachian tube balloon dilation, and the degree of improvement is not linearly related to the postoperative time.
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OBJECTIVE Aim to explore the value and the selection of observation target of P1 component in children with cochlear implant(CI). METHODS 13 children(4.37±0.73 years old) with right side CI and one year of regular post-CI rehabilitation were recruited as CI group. 15 gender and age (4.25±0.84)years matched children with left side external and middle ear malformation were selected as control group. We collected their AEP which showed their reaction to 1000 Hz pure tone and analyzed the P1 component. RESULTS The cut off value between CI group and control groupwas 10.4mV for P1 Amplitude(P1A) and 110.5 mV for P1 Latency(P1L). More precisely, the values of CI group were above the cut off value while the values of control group were below it. Whether choosing P1A or P1L as dividing standard, the AUC were between 0.5 and 0.9(AUC: P1A0.733, P1L0.800), which showed medium distinguishing significance. P1L component showed greater You-den index(0.590>0.471) and sensitivity(0.923> 0.538) while P1A showed greater specificity(0.933>0.667). CONCLUSION P1L shows greater ability in distinguishing the difference between CI group and control group while P1A has advantage in determining their common feature. Generally, P1L shows higher value in studying CI children. We need to make choice between P1A and P1L in different situation and use P1A and P1L standard in series or parallel.
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Inherited bone marrow failure syndromes are a group of congenital diseases.Their pathogenesis are not entirely clear.The causative genes have been found in part of the diseases, and we have preliminarily mastered their diagnosis and treatment.The diagnosis is mostly based on typical clinical manifestations and related laboratory tests.Along with the genetic testing developmenff,genetic testing has become the main method to diagnose IBMFS.Hematopoietic stem cell transplantation is currently the only way to cure these diseases.Support and symptomatic treatment also play an important role in terms of delaying and improving the condition.Gene therapy is still not mature, and other treatments are constantly being explored.
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Objective To investigate the value of 64-slice spiral CT angiography in diagnosis of the origin of abdominal large masses.Methods Twenty patients who were proven by operation and pathology to be abdominal massive tumor were collected in this study,tumor diameter average 17.8cm.All patients accepted plain and enhanced CT scanning,and their data were transferred to Philips IntelliSpace Portal.The tumor vessel were reconstructed with multiplanar reformation(MPR),maximum intensity projection(MIP),and volume rendering(VR).The origin of tumor were judged according to the feeding arteries by 2 attending physician,and the results were compared with pathology.Results Of these 20 cases,15 cases were malignant tumor,5 benign.Blood supply arteries were found in 19 patients,36 vessels.Lateral branch vessels in 6 cases and arteriovenous fistula in 4 cases.MSCTA findings were consistent with operation and pathology,with the accuracy of 90%.One case had no tumor vessel,one was misdiagnosed.Conclusion MSCT could be taken good use in diagnosis of large abdominal masses by tracking down the nourishing artery of masses.
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Aim To determine the neuroprotective effect of sulfated pachymaran (SP)on MPTP-induced mouse model.Method ICR mice were randomly di-vided into control group,MPTP group and SP treatment group (50,1 00,1 50 mg·kg -1 ,ip).After 1 7 days, the activities of endogenous antioxidants (SOD,GSH-Px,CAT),antisuperoxide anion,hydrogen peroxide and MDA content in the midbrain and cortex were as-sayed.Results The results proved that SP significant-ly reduced the content of MDA and H2 O2 ,regulated the activities of antioxidant enzyme and increased the activity of antisuperoxide anion.Conclusion All these effects indicate that SP is a potential neuroprotective a-gent and its neuroprotective effects are achieved in the MPTP mouse model.
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Objective To evaluate the detection rate of multi-slice spiral CT (MSCT)signs and the clinical value of multi-planar reconstruction (MPR)in T1a and T1b peripheral lung cancer patients.Methods Eighty-seven cases with peripheral lung cancer proved by pathology were collected.The cases were divided into T1a and T1b group based on the TNM classification.The MSCT and MPR images were compared between the two groups.Results (1)Detection rate of the deep sublobe sign,spinous process sign, short spiculated sign,pleural indentation sign,vascular convergence sign,multi-nodule accumulation sign,vacuole sign and air bron-chogram sign,were 1 1.4%,20.0%,31.4%,60.0%,25.7%,45.7%,42.9% in T1a group and 42.3%,36.5%,57.7%, 80.8%,5 1.9%,25.0%,21.2% in T1b group,respectively.The difference were all statistically significant (P < 0.05)between T1a and T1b group except that of the spiculated sign (P = 0.098).(2)The detection rate of the sublobe sign,spinous process sign, spiculated sign,pleural indentation sign and vascular convergence sign were higher on MPR images than on axial thin-slice images in both T1a and T1b group.Conclusion The detection rate of the tumor-lung interface’s signs are lower in T1a than in T1b,the detec-tion rate of internal structure signs of the tumor are higher in T1a than in T1b in peripheral lung cancer patients.MPR has important value in early diagnosis of peripheral lung cancer.
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This study aimed to explore the cognitive dysfunction of and hippocampal neuron damage to Wistar rats with STZ-induced diabetes at different morbidity time. All Wistar rats in the tests received intraperitoneal injections of streptozotocin (STZ; 60 mg/kg) to induce type 1 diabetes. The concentration of blood glucose and the body weight were investigated, the cognitive ability of rats was assessed using a standardized Y-maze, and the apoptotic neurons in the CA1 of the hippocampus were also examined by using the HE staining. While the sickening time was prolonged, the blood glucose concentration of the experimental rats increased continuously and the body weight decreased. On the 70th day after STZ administration, the neuronal loss in the hippocampal CA1 region increased and the working errors increased in rats with the diabetes. The results showed that Wistar rats could complicate with diabetic encephalopathy in 70 days after injection of STZ for inducing the diabetes.
Subject(s)
Animals , Rats , Blood Glucose , Body Weight , CA1 Region, Hippocampal , Cell Biology , Pathology , Cognition , Cognition Disorders , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 1 , Neurons , Pathology , Rats, Wistar , Streptozocin摘要
<p><b>OBJECTIVE</b>To determine the effects of ginsenosides Rb1(GSRb1) on learning and memory and expression of somatostatin (SS) in the hippocampus and the frontal cortex in rat model of sleep deprivation (SD).</p><p><b>METHODS</b>Rats were randomized into groups of SD 2 d, SD 4 d, SD 6 d, and SD 0 d, while each group was sub-divided into GSRb1 group and normal saline (NS) sub-groups. Rats were intraperitoneal administered with 30 mg/(kg*d) of GSRb1 or NS for 7 d, then the learning and memory abilities were examined by measuring average swimming speed and mean escape latency using Morris maze.Expression of somatostatin was detected with immunohistochemical method and image analysis in the hippocampus and the frontal cortex.</p><p><b>RESULTS</b>Compared with SD 0 d rats, SD rats exhibited significant decrease in the average swimming speed and increase in the escape latency (P <0.01). The expression of somatostatin in the hippocampus was decreased significantly in SD 2 d, SD 4 d and SD 6 d rats (P<0.05). However, decrease was only observed in SD 4 d and SD 6 d rats in the frontal cortex (P <0.05). Parallel comparison between NS control and GSRb1 treated rats demonstrated that rats treated with GSRb1 in each subgroup exhibited faster swimming speed and shorter escape latency (P <0.05). Meanwhile, the expression of somatostatin was increased in SD 2 d, SD 4 d and SD 6 d rats in the hippocampus and in SD 4 d and SD 6 d rats in the frontal cortex (P <0.05), respectively.</p><p><b>CONCLUSION</b>GSRb1 enhances the expression of somatostatin in sleep deprivation rats and subsequently may improve learning and memory abilities of rats.</p>
Subject(s)
Animals , Male , Rats , Brain , Metabolism , Disease Models, Animal , Ginsenosides , Pharmacology , Learning , Memory , Rats, Sprague-Dawley , Sleep Deprivation , Metabolism , Somatostatin , Metabolism摘要
Objective To investigate the effect of insulin resistance(IR) on the persons with abnormal blood glucose who underwent dietary interventions.Methods 194 individuals with abnormal blood glucose were selected from hyperlipidemia population taking the community intervention program in districts of Beijing.The insulin resistance and insulin action index(IAI) were calculated with fasting blood glucose(FBG) and fasting blood insulin(FINS),and analyzed the relationship of variety on their blood glucose,serum lipids and body weight,body mass index(BMI),waist circumference,waist hip ratio(WHR).Results 1) Blood glucose(FBG),triglyceride(TG),waist circumference and WHR had significant positive relationship with IR but negative with IAI;2) In the intervention group,FBG and TG were reduced significantly in the subgroup with highest IAI.Conclusions IR was related with blood glucose,serum lipids,waist circumference and WHR,but no significant relation with body weight and BMI;It was possible that IR had some effect on dietary intervention.
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Objective To investigate a possible role of orexin in the regulation of estrous cycle by examining the expression of orexin and orexin receptors(OX1R,OX2R) in the rat hypothalamus during the estrous cycle. Methods The levels of prepro-orexin(prepro-OX),orexin-A,OX1R,and OX2R in the rat hypothalamus during the estrous cycle were evaluated by competitive reverse transcription-polymerase china reaction(RT-PCR) assay. Results Only expression OX1R mRNA during late proestrus was significantly higher than that at metestrus.No significant changes of prepro-OX and OX2R mRNA expression were observed during the various estrous cycle phases.Conclusion Orexin might regulate the secretion of GnRH and/or LH by binding OX1R,contributing to the occurrence of ovulation.
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Objective To investigate the possible role of orexin in reproduction and examine the changes in the expression of orexin and its receptors(OX1R,OX2R) in the rat hypothalamus during pregnancy,parturition and lactation. Methods The expressions of prepro-orexin(prepro-OX),orexin-A,OX1R,and OX2R in the rat hypothalamus during pregnancy,parturition,and lactation were evaluated by competitive reverse transcription-polymerase chain reaction(RT-PCR) and immunohistochemistry assay. Results Orexin-A immunoreactive(ir) neurons and the OX1R subtype in neuronal cell bodies were mainly located in the lateral hypothalamic area(LHA) as well as in the magnocellular neurons of the paraventricular and supraoptic nuclei respectively in pregnant and lactating rats.The prepro-OX and OX1R mRNA levels on the 1st day of lactation were significantly higher than that during late pregnancy and lactation.No significant changes of OX2R expression were observed during the various reproductive phases.Conclusion Orexin might be involved in regulating reproductive function in early lactation through their binding sites in hypothalamic PVN and SON.