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Whether direct manipulation of Parkinson's disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6-10 months), and thus provides a practical transgenic monkey model for future PD studies.
Subject(s)
Animals , Brain , CRISPR-Cas Systems/genetics , Dependovirus/genetics , Haplorhini , Phenotype , Protein Kinases/geneticsABSTRACT
Whether direct manipulation of Parkinson’s disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6–10 months), and thus provides a practical transgenic monkey model for future PD studies.
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Objective:Based on the detection of CD4+IL17+Th17 and CD4+CD25+Foxp3+Treg cells in the peripheral blood of patients with human papilloma virus (HPV), the study analyzes the ratio of Th17 to Treg and compares the different expression of cytokine IL-17, IL-10, TGF-β, and IL-23 in the serum. Methods:From September 2014 to June 2016, 119 cases of untreated patients with cervical HPV in-fection were collected at the First Affiliated Hospital of Xinjiang Medical University, which include 46 cases of cervical cancer (CC), 43 cases with cervical intraepithelial neoplasia (CIN)Ⅱ-Ⅲ, and 30 with chronic cervicitis (CCS). The detection of HPV types classified 80 patients as high-risk and 39 as low-risk. Flow cytometry examined Treg and Th17 cells, and enzyme-linked immune sorbent assay was used to test related cytokines. Results:In the infection of high-risk cervical HPV, the rate of the CC group was 87%(40/46), which was higher than that of the CINⅡ-Ⅲgroup and the CCS group, which were 77%(33/43) and 23%(7/30), respectively. For the expression of Th17 and Treg cells in the peripheral blood and the related cytokine IL-17, IL-23, TGF-β, and IL-10 in the serum, the levels of CC group were also significantly higher than that of the other two groups, and the ratio of Th17 to Treg increased considerably with the se-verity of cervical lesions. The expression of Th17 and Treg cells in the peripheral blood of patients with high-risk cervical HPV were higher than that of patients with low-risk cervical HPV (P<0.05), which was the same for the expression of the related cytokine IL-17, IL-23, TGF-β, and IL-10 in the serum. The ratio of the Th17 to Treg of patients with high-risk cervical HPV increased remarkably (P<0.05). Conclusion:The expression of Treg and Th17 cells in high-risk patients exhibits an increasing trend, and the ratio of increased Th17 to Treg may directly participate in the process of HPV infection and immune evasion, which plays an important role in the occurrence and development of cervical cancer.
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<p><b>OBJECTIVE</b>To evaluate the clinical effectiveness of tooth-alveolar bone grafts in repairing dentition defects.</p><p><b>METHODS</b>Forty-five patients with dentition defect were divided into two groups according to different operation methods. In group A (n=24), the tooth-alveolar bone grafts of the transplanted tooth and its surrounding alveolar bone were cut using modified surgical orthodontics and then embedded into the designated planting hole. In group B (n=21), the teeth were extracted through conventional tooth transplantation and then embedded into the prepared planting holes. The transplanted teeth were fixed for about 4-6 weeks using the orthodontic method. During the postoperation, which lasted for 2-12 weeks, root canal treatments were administered selectively. The medical effect was regularly followed up and evaluated.</p><p><b>RESULTS</b>No significant difference was found in the change of color and the periodontal ligament image between the two groups (P>0.05) whereas significant differences were observed in the degree of tooth mobility, the absorption of root and alveolar bone, and the rate of root canal treatment (P<0.05). The curative effect in group A was superior to group B.</p><p><b>CONCLUSIONS</b>Tooth-alveolar bone graft transplantation has overcome some of the limitations of traditional tooth transplantation. Therefore, it is an effective means of repairing dentition defect.</p>
Subject(s)
Humans , Alveolar Bone Grafting , Dentition , Periodontal Ligament , Tooth , Tooth RootABSTRACT
Objective To observe the effective outcome of application of Ruyi golden powder and magnesium sulfate in the treatment of phlebitis caused by amiodarrone.Methods 60 patients were randomly divided into the observation group and the control group (30 cases in each group).The external application of Ruyi golden powder which was prepared with 75％ alcohol into a paste was used in the observation group and 50％ magnesium sulphate was used in the control group.Results The total effective rate of two groups of patients was 93.3％ in the observation group and 66.7％ in the control group,the significant difference was found by the comparison of the two groups.Conclusions The external application of Ruyi golden powder with alcohol in the treatment of phlebitis caused by amiodarrone is better than magnesium sulfate.
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Objective To investigate the regulatory effect of hydrogen sulfide (H2S) on endoplasmic reticulum stress (ERS) and lipid metabolism in livers in apoE knockout (apo E-/-) mice.Methods Male C57BL/6 J mice and homozygous apoE mice were fed with a western type diet and randomly divided into four groups:C57BL/6 J control group (injected intraperitoneally with normal saline),apoE group (injected intraperitoneally with normal saline),apoE-/-+NaHS group (injected intraperitoneally with an H2S donor NaHS 56μmol · kg-1 · d-1) and apoE-/-+ DL-propargylglycine (PPG) group (injected intraperitoneally with an acystathionine-γ-lyase inhibitor PPG 30 mg ·kg-1 · d-1).After 10 weeks,all mice were sacrificed and plasma lipids were detected.Lipid deposition was determined by oil red O staining.Glucose-regulated protein78 (GRP78),Thr-981 phosphorylated double-stranded RNA-activated protein kinase like endoplasmic reticulum kinase (PERK),subunit of eukaryotic translation initiation factor-2α (elF-2α),low density lipoprotein (LDL) receptor (LDLR),sterol regulatory element binding protein-2 (SREBP-2) in the livers were detected by Western bloting.The expressions of GRP78 and SREBP-2 mRNA were analyzed by realtime polymerase chain reaction (RT-PCR).Results Compared with C57BL/6 J control group,plasma levels of total cholesterol (TC),triglyceride (TG) and low density lipoprotein (LDL),liver lipid content and expressions of GRP-78,PERK and eIF-2α were significantly increased in apoE-/-mice,but body weight did not change.Compared with apoE-/-mice,plasma LDL level was decreased,liver lipid deposition was improved,expressions of GRP-78 and PERK in livers were increased,and the ratio of p-eIF-2α/ eIF-2α was increased in apoE-/-+NaHS group,but expression levels of SREBP-2 and LDLR in liver did not change.Conclusions H2S decreases serum LDL level and liver lipid content,and up regulates GRP78 protein and mRNA expressions,promotes PERK and eIF2α phosphorylations,improves endoplasmic reticulum function,but has no effect on the expressions of SREBP-2 and LDLR in apoE-/-mice fed with a high-fat diet.
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Objective To explore the influence of human resources management in emergency department on nurse's anxiety.Methods Self-Rating Anxiety Scale(SAS)was used to investigate 300 nurses in the emergency department in nine secondary level hospitals of Longgang District.Division of human resource management in these hospitals were examined and the correlation between them was statistically analyzed.Results In addition to the three hospitals,nurses anxiety status of the other six hospitals score showed different levels of anxiety,the average scores were above 50,but the hospitals,that the ratio of the three anxiety condition score was less than 50,moderate to severe anxiety were still more than 20.0％,and other six hospitals was up to 66.7％.In the human resource management to achieve excellent and qualified hospital,the anxiety rate was significantly lower than the substandard hospitals.At the same time there was close correlation between the situation of human resource management and nurses anxiety situation.Conclusions Emergency nurses generally have high anxiety,and in hospitals with poor human resource management,career anxiety is even more obvious.That is to say the anxiety of nurses is closely related to emergency department management of human resources.
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Aim To observe the intervention effects of sodium aescinate on acute lung injury model of rats induced by oleate. Methods Fifty four male SD rats were randomly divided into five groups: normal control group, sodium aescinate control group (without oleate) , oleate model control group,medrol interventional group and sodium aescinate interventional group. Acute lung injury models of rats were made by injecting oleate (OA, 0. 1 ml · kg~(-1) ) through caudal veins, and then rats were observed and killed to detect correlated in-dice. The observation indice were the histomorphology of lung, the wet and dry weights of lung ( W/D), score of injury of lung under light microscope (IQA ) , partial pressure of oxygen in artery ( PaO_2) , the levels of SOD and MDA in blood plasma and lung tissue. Results ① Histomorphology of lung: Lung surface hyperemia relieved obviously and pink secretion from trachea of rats in sodium aescinate interventional group and medrol interventioal group decreased significantly compared with oleate model control group. Under light microscope , compared with oleate model control group, effusion of inflammatory cells in alveolar space of rats in sodium aescinate interventional group and medrol interventional group decreased. ② The wet and dry weights of lung ( W/D ) ; W/D of rats in oleate control model group increased obviously compared with those in normal control group, W/D of rats in sodium aescinate interventional group and medrol interventional group decreased obviously compared with those in oleate model control group. ③ Score of injury of lungs under light microscope (IQA) ; IQA of rats in oleate model control group advanced obviously compared with that in normal control group. IQA of rats in sodium aescinate interventional group and medrol interventional group lowered significantly compared with that in oleate model control group.④ Partial pressure of oxygen in artery (PaO_2) : PaO_2 of rats in oleate model control group lowered significantly compared with that in normal control group. PaO_2 of rats in sodium aescinate interventional group and medrol interventional group improved significantly compared with that in oleate model control group. ⑤ The levels of SOD and MDA in blood plasma and lung tissue:The levels of SOD in plasma and lung tissue of rats in oleate model control group lowered significantly compared with those in normal control group. SOD in plasma and lung tissue of rats in sodium aescinate in-terventional group and medrol interventional group increased significantly compared with that in oleate model control group. The levels of MDA in plasma and lung tissue of rats in oleate model control group lowered significantly compared with those in normal control group. MDA in plasma and lung tissue of rats in sodium aescinate interventional group and medrol interventional group increased significantly compared with that in oleate model control group. Conclusion Sodium aescinate can improve W/D, IQA and PaO_2 by adjusting oxidization of the acute lung injury model of rats, which may provide a possible path for treating acute lung injury in clinical practice.
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Objective To study the effect of whole-process nursing intervention on comfort of patients undergoing radial artery puncture. Methods 100 patients with radial artery puncture from July, 2007 to June, 2008 were divided into the control group and the experimental group with 50 cases in each group accord-ing to time sequence. Routine whole nursing mode was used in the control group, the whole-process nursing intervention mode based upon routine nursing mode under the instruction of evidence-based method was used in the experimental group. Pain, psychological tensity, body numbness, success rate of radial artery puncture, patients' satisfaction degree were compared between the two groups. Results Every indexes of the experi-mental group were better than those of the control group. Conclusions The whole-process nursing interven-tion mode can promote the comfort degree of patients undergoing radial artery puncture.
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Objective: To evaluate the reliability and effects of a compound bone substitute materials Bio-oss artificial bone grafts with recombinant human bone morphogenic protein-2(rhBMP-2) filling the alveolar bone defects around heterogenous replanted teeth. Methods:3 dogs′ bilateral mandible 3rd premolars(6 sites) were extracted. The defect sites without buccal and lingual alveolar bone were prepared for the heterogenous implanted teeth and the compound of Bio-oss and rhBMP-2 filled the alveolar bone defects around. The bone regeneration was observed by naked eye, radiograph, histology and histomorphometric analysis after 2, 3 months. Results:The new alveolar bone showed osteogenesis and calcification after 2 months, and intergrated with implanted teeth root under the light microscope and X ray. The new bone trabecular thickness(Tb.Th) augmented continuously. Differences of the bone area(B.Ar) and bone perimeter(B.Pm) were statistically significant after 2nd and 3rd month(P
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ⅳ Hydroxyl scavenger, mannitol, in the dosage of 1.1mol/L 2g/kg and 3g/kg could increase LD_(100) of ouabain on guineapigs from 298.54?33.30 ?g/kg to 367.44?44.58 ?g/kg (P
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Recently, it had been demonstrated that some free radical scavengers, reduced glutathion ( GSH ) , Ascorbic acid(AA), the purified aponin Rg1andRb1 of Panax notoginseng, Sodium selenate