ABSTRACT
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.
ABSTRACT
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
To evaluate the therapeutic effect of using micro-implant anchorage (MIA) to rotate the functional occlusal plane (FOP) counterclockwise. Forty skeletal class Ⅱ high-angle patients who had completed orthodontic treatment were enrolled, including 20 patients treated with MIA orthodontic system (MIA group) and the other 20 patients treated with traditional sliding straight wire appliance (control group). Cephalometric measurements on the lateral cranial radiographs before and after treatment were performed, all acquired data were statistically analyzed with SPSS 26.0. At the end of treatment, MIA group obtained better effect of FOP and mandibular plane counter-clockwise rotation than the control group. In the MIA group, the average change of FOP-frankfort horizontal plane (FH), FOP-SN and mandibular plane angle (MP-FH) angle was -4.5(-7.3, -3.7)°, (3.3)° and -1.7(-3.0, -0.9)°, respectively. In the control group, the average change of FOP-FH, FOP-SN and MP-FH angle was -0.1(-4.1, 3.0)°, (-0.1±5.1)° and -0.4(-2.4, 0.7)°, respectively. There was significant difference between the change of the two groups (all <0.05). Compared with the traditional sliding straight wire appliance, counterclockwise rotation of FOP can be more effectively reversed by using MIA orthodontic system, and the MP-FH can be reduced as well.
Subject(s)
Humans , Cephalometry , Dental Occlusion , Malocclusion, Angle Class II/therapy , Mandible , Maxilla , Treatment OutcomeABSTRACT
Objective:To explore the application value and initial clinical experience of fluorescence-enhanced laparoscopy combined with indocyanine green in radical cystectomy with pelvic lymphadenectomy.Methods:A retrospective analysis was performed on the clinical data of a total of 8 patients admitted from May 2018 to August 2019 who underwent laparoscopic radical cystectomy with pelvic lymphadenectomy for muscle-invasive bladder cancer using the fluorescent laparoscopy system.There were 6 males and 2 females; aged 58 to 71 years, with an average of 65.8 years. The preoperative pathology was urothelial carcinoma, with 2 cases in T 2a stage, 4 cases in T 2b stage, and 2 cases in T 3a stage. The patient was injected a total of 2 ml of 2.5 mg/ml of indocyanine green through a rigid cystoscope using a 18 gauge cystoscope injection needle before surgery. The PINPOINT endoscopic fluorescence camera system performed surgery in real-time. A systematic examination of the surgical area under near-infrared fluorescence was performed every 5 minutes. Observation and recording of indocyanine green combined with fluorescence laparoscopy to mark the bladder tumor area and identify the sentinel drainage. Results:Eight cases were successfully completed under the fluorescence laparoscopic system.In terms of tumor markers, cystoscopy with indocyanine green allowed 7 of the 8 patients to successfully identify the tumor area under fluorescent laparoscopy. Six of the 8 patients with sentinel lymph nodes identified by indocyanine green lymphangiography were also successful, of which 3 were positive for lymph nodes. At the same time, intravenous indocyanine green was used to observe that the blood supply to the bladder and the end of the ureter was good. The operation time was 190-310 minutes, with an average of 235 minutes; the bleeding volume was 150-380 ml, with an average of 180 ml; the postoperative hospital stay was 10-22 days, with an average of 14.5 days. Postoperative pathological staging 2 cases in T 2a stage, 3 cases in T 2b stage, 3 cases in T 3a stage, with total number of lymph nodes 8-14, average 10. The 8 cases were followed-up for 4-12 months, average 5.5 months, without indocyanine green related complications. Conclusions:Indocyanine green fluorescent laparoscopy can accurately locate and identify the bladder tumor area and pelvic lymph nodes during radical cystectomy, which can reduce positive margins and unnecessary enlarged lymph node dissection.
ABSTRACT
Objective To investigate the diagnosis and treatment of cystic renal cell carcinoma.Methods The clinical data of 67 cases of cystic renal cell carcinoma treated from January 2005 to April 2013 were analyzed retrospectively.Preoperative imaging procedures indicated masses of renal cysts in 67 cases,including malignant tumors in 59 cases.Intraoperative pathological examination was performed in 59 cases and the pathological results showed malignant tumors in 56 cases,renal cyst in 2 cases and multilocular cyst of kidney in 1 case.The surgical procedures included radical nephrectomy (n=19),partial nephrectomy (n =12),retroperitoneal laparoscopic radical nephrectomy (n =9),retroperitoneal laparoscopic partial nephrectomy (n =20),retroperitoneal laparoscopic cyst unroofed then transferred to radical nephrectomy (n =6),and retroperitoneal laparoscopic partial nephrectomy transferred to radical nephrectomy (n =1).Results The 67 cases were diagnosed as renal carcinoma,including clear renal cell carcinoma with cystic changes in 31 cases and multilocular renal cell carcinoma in 36 cases.Sixty-two cases were followed up for 10-110 months (median 56 months),and there was no recurrence or metastasis,among which 7 cases diagnosed as benign pre-operation or intra-operation but malignant by pathological examination after surgery were followed up for 61-103 months (median 82 months).Conclusions Imaging plays an important role in the early diagnosis of cystic renal cell carcinoma.Intraoperative pathological examination should be performed in suspected cases.Nephron-sparing surgery is preferred with good outcome.
ABSTRACT
Objective To study the imaging features of Scheuermann disease and compare the value of MRI, X-Ray and CT images in diagnosis of this disease. Methods The images of 14 Scheuermann disease patients were analyzed retrospectively. Results The pathological changed vertebraes have wedge-shaped changes in different degree. The edges of the vertebraes manifest roughness and have become step-shaped, or Schmorl′s nodes were demonstrated. Conclusion The multi-vertebraes wedge-shaped changes and the Schmorl′s nodes are the main imaging features of Scheuermann disease. The pathological change occurs in the different spine segments, and the imaging features are not completely same. X-Ray and MRI images are more important in diagnosis of this disease. MRI Multi-direction imaging displays clearly the Schmorl′s nodes, marrow dropsy, the fat accumulation and the intervertebral disc denaturation. What′s more important is that MRI has its own superiority in the differential diagnosis of this disease.